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BMC Oral Health

, 19:246 | Cite as

Composition and diversity of the subgingival microbiome and its relationship with age in postmenopausal women: an epidemiologic investigation

  • Michael J. LaMonteEmail author
  • Robert J. Genco
  • Michael J. Buck
  • Daniel I. McSkimming
  • Lu Li
  • Kathleen M. Hovey
  • Christopher A. Andrews
  • Wei Zheng
  • Yijun Sun
  • Amy E. Millen
  • Maria Tsompana
  • Hailey R. Banack
  • Jean Wactawski-Wende
Open Access
Research article
Part of the following topical collections:
  1. Epidemiology of oral health

Abstract

Background

The extent to which the composition and diversity of the oral microbiome varies with age is not clearly understood.

Methods

The 16S rRNA gene of subgingival plaque in 1219 women, aged 53–81 years, was sequenced and its taxonomy annotated against the Human Oral Microbiome Database (v.14.5). Composition of the subgingival microbiome was described in terms of centered log(2)-ratio (CLR) transformed OTU values, relative abundance, and prevalence. Correlations between microbiota abundance and age were evelauted using Pearson Product Moment correlations. P-values were corrected for multiple testing using the Bonferroni method.

Results

Of the 267 species identified overall, Veillonella dispar was the most abundant bacteria when described by CLR OTU (mean 8.3) or relative abundance (mean 8.9%); whereas Streptococcus oralis, Veillonella dispar and Veillonella parvula were most prevalent (100%, all) when described as being present at any amount. Linear correlations between age and several CLR OTUs (Pearson r = − 0.18 to 0.18), of which 82 (31%) achieved statistical significance (P < 0.05). The correlations lost significance following Bonferroni correction. Twelve species that differed across age groups (each corrected P < 0.05); 5 (42%) were higher in women ages 50–59 compared to ≥70 (corrected P < 0.05), and 7 (48%) were higher in women 70 years and older.

Conclusions

We identified associations between several bacterial species and age across the age range of postmenopausal women studied. Understanding the functions of these bacteria could identify intervention targets to enhance oral health in later life.

Keywords

Aging Women Oral Microbiome Epidemiology 

Abbreviations

CLR

Centered-log(2)-ratio

OTU

Operational Taxonomic Unit

Background

The availability of high throughput metagenomics sequencing technology has allowed for deeper understanding of complex microbiota ecologies and their aggregate functional capacities within a defined microbiome [1, 2]. Marked differences in composition and function of microbiomes have been shown between various body sites among individuals [3, 4]. It has become increasingly clear that the microbiota and microbiome are correlated with both health and disease states in humans [5], and that the aging process could be an important determinant of these relationships [6, 7]. Aging is a complex, multifactorial process characterized by progressively lower resilience to stress, increased homeostatic imbalance, and greater susceptibility to pathologic insult and disease onset [8]. Changes in microbiome diversity and function have been observed with increasing age [9]. Alterations in the host environment that occur with physiologic aging processes could enable untoward shifts in relative abundance of commensal and pathogenic bacteria, and enhanced expression of pathogen genomes which, in turn, could heighten disease susceptibility. In support of this hypothesis are studies demonstrating links between human microbiomes and several diseases of aging including obesity, diabetes, heart disease, and certain cancers [5, 7, 10].

The oral microbiota comprise one of the most complex and diverse human microbiomes [3, 11, 12]. Oral bacteria have important functional roles that contribute to maintenance of oral health [13], to oral diseases such as caries and periodontitis in the setting of dysbiosis [14, 15], and potentially to systemic diseases of aging by way of bacterial translocation through ulcerated oral epithelium, aspiration, or ingestion [7, 16]. This could have important implications to public health given the rapid growth in numbers of older adults expected in coming decades.

Surprisingly, there exists a limited understanding of oral microbiota in aging populations. Feres et al. [17] conducted a comprehensive review of published literature and concluded that the majority of oral microbiome studies have included younger and middle-aged adults. Only a small number of studies have described the microbiome in older adults, among which sample sizes of adults 60 years and older tended to be, on average, modest (e.g., < 200), the majority of whom were men and were selected to have moderate to severe periodontitis [17, 18, 19]. A majority of previous studies have used low throughput microbial measurement techniques, such as microbial culture and targeted DNA probes, which result in an incomplete characterization of the oral microbiome composition and diversity in relationship to groups of men and women of differing ages. Recent investigations have extended these previous studies by using next generation sequencing methods, but again relatively small sample sizes (< 100) limited the contrasts that could be performed in relation to age in the majority of these studies [20, 21, 22, 23].

Thus, at present, an incomplete understanding of the composition and characteristics of the oral microbiome exists in the context of aging, particularly in women. A critical step in advancing knowledge on how the oral microbiome relates with the frequency of oral (e.g., periodontitis) or systemic (e.g., breast cancer) diseases of aging, is to first understand the extent of the composition and how the microbiota vary with host characteristics, such as age. This information will be important in later understanding the interplay of the microbiome with pathogenic changes over time. Application of epidemiologic study methods to study populations not selected on disease status is a suggested approach to establish a foundational understanding of microbiome diversity expected in a population that then allow for hypotheses pertaining to disease-related variation that can then be accurately evaluated [24]. The objective of this current cross-sectional investigation was to describe the composition and diversity of the subgingival plaque microbiome and its relationship with age in a cohort of ambulatory postmenopausal women, aged 53–81 years, who were enrolled in an ongoing study from the community dwelling women without selection on periodontal health status at enrollment.

Methods

Participants

The present study included 1219 postmenopausal women enrolled in the Buffalo Osteoporosis and Periodontitis (OsteoPerio) Study, which is an ancillary study conducted at the Buffalo (NY) clinical center of the Women’s Health Initiative Observational Study (WHI OS). Participants provided written informed consent for all components of the studies, which were conducted in accord with the Helsinki Declaration on human subjects research. Experimental protocols for all aspects of the WHI study, the OsteoPerio Study, and the microbiome study detailed in this paper were approved by the Institutional Review Board at the University at Buffalo. This manuscript conforms to the STROBE guidelines for human observational studies. Details about recruitment, enrollment criteria, study implementation and measurements have been published for the WHI OS [25] and the OsteoPerio study [26, 27]. Briefly, 2249 postmenopausal women, ages 50–79, enrolled into the WHI OS at the Buffalo center between 1994 and 1998. Of these, 1362 enrolled into the OsteoPerio study 3 years later in 1997–2001 (mean age 66; range 53–81 years). Enrollment into the OsteoPerio study required at least 6 teeth present and no history of bone disease other than osteoporosis and no history of cancer in the previous 10 years. Women completed standardized questionnaires pertaining to demographic information, lifestyle habits, and personal health history, as well as undertaking a whole mouth oral examination conducted by trained and calibrated examiners. Neighborhood socioeconomic status was derived from questionnaire responses and census tract information [28]. Detailed descriptions of the oral examination measures and their reproducibility have been published [26]. Figure 1 shows a flow chart of participant enrollment into the OsteoPerio study.
Fig. 1

Flow of participants into the Buffalo OsteoPerio Study

Subgingival plaque samples

A protocol for obtaining subgingival plaque samples was developed for this study and has been published [29]. Fine paper points – (#504; Henry Schein, Melville, NY) were placed in the gingival pockets of up to 12 pre-specified teeth (6 maxillary and 6 mandibular arch teeth) for 10 S. index teeth [3, 5, 7, 9, 12, 14, 19, 21, 23, 25, 28, 30, and] were usually sampled. Alternative teeth [2, 4, 8, 10, 13, 15, 18, 20, 24, 26, 29, 31, and] were used if the corresponding index tooth was missing. Paper points containing all subgingival plaque samples from each arch were placed directly into 4 mL lactated Ringer’s solution. The solution was taken to the lab where it was vortexed for dispersion of microorganisms, placed in cryogenic straws, frozen immediately at -80 °C and later placed in cryogenic tanks at -196 °C as previously described [29]. Before next generation sequencing, samples were placed in − 80 freezers and later thawed, with upper and lower arch samples combined into a single aliquot for the purpose of sequencing.

DNA isolation and purification

Genomic DNA was isolated using the QIAsymphony SP automated system (Qiagen, Valencia, CA) with the QIAsymphony DSP Virus/Pathogen Mini Kit (Qiagen, Valencia, CA) and the Complex200_V6_DSP protocol after enzymatic pretreatment. In detail, 500 μl of oral plaque solution contained in a barcoded 2 ml tube was equilibrated at room temperature (15-25 °C). Bacteria was pelleted by centrifugation at 5000×g for 10 min, resuspended in a 300 μl lysis solution (20 mg/ml lysozyme in 20 mM Tris-HCl, pH 8.0; 2 mM EDTA; 1.2% Triton X-100) and incubated at 37 °C for 30 min. Following incubation, tubes were briefly centrifuged to remove drops from inside the lid and then placed in the tube carrier of the QIAsymphony SP.

DNA extraction and purification was done according to the Qiasymphony DSP Virus /Pathogen Kit Instructions. Carrier RNA-AVE mixture was added to all samples for increased recovery of nucleic acids. After DNA purification, samples were eluted in a barcoded 96 well elution plate (Qiagen, Valencia, CA). All batches of samples were performed with DNA extraction negative controls and positive controls from a single large pool of mixed plaque samples.

16S rRNA amplification and sequencing

Metagenomic amplification of the extracted DNA for 16S amplification of the V3–V4 hypervariable region proceeded following the Illumina manufacturer protocol (Illumina Inc., San Diego, CA) with modifications developed for our study [30]. The Illumina protocol relies on limited cycle PCR for addition of Illumina sequencing adapters and dual-index barcodes to the 16S rRNA V3-V4 ampli. We also included as part of the 96-well plates, samples of the UltraClean DNA free PCR water (MO BIO Laboratories, Carlsbad, CA) and RNase/DNase free water (Ambion, Foster City, CA) as negative controls, and genomic DNA from microbial community HM-277D (microbial community B; BEI Resources; Manassas, VA) as a positive control during the amplification process. Metagenomic DNA was amplified using the 16S V3 (341F) forward and V4 (805R) reverse primer pairs with added Illumina adapter overhang nucleotide sequences. Amplicon PCR was completed with 42 μl of genomic DNA, 4 μl of amplicon PCR forward primer (5 μM), 4 μl of amplicon PCR reverse primer (5 μM), and 50 μl of 2x KAPA HiFi HotStart Ready Mix (KapaBiosystems) at 95 °C initial denaturation for 3 min, followed by 25 cycles of 95 °C for 30 s, 62.3 °C for 30 s, and 72 °C for 30 s, and a final extension at 72 °C for 5 min. Reactions were cleaned with Agencourt AMPure XP beads (Beckman Coulter Genomics, South Plainfield, NJ) according to the manufacturer’ s protocol.

Library generation was performed using 5 μl of amplicon PCR product DNA, 5 μl of Illumina Nextera XT Index Primer 1 (N7xx), 5 μl of Nextera XTIndex Primer 2 (S5xx), 25 μ l of 2x KAPA HiFi HotStart Ready Mix, and 10 μl of PCR-grade water (UltraClean MO BIO Laboratories, Inc.), with thermocycling at 95 °C for 3 min, followed by 8 cycles of 95 °C for 30 s, 55 °C for 30 s, and 72 °C for 30 s, and a final extension at 72 °C for 5 min. 16S metagenomic libraries were purified with Agencourt AMPure XP beads and quantified with Quant-iT PicoGreen. Nextera index primer sets (A, B, and C) were rotated for each batch to reduce sequence carryover between MiSeq runs.

Library quality control was performed with the Fragment Analyzer (Advanced Analytical Technologies, Inc., Ankeny, IA) to ascertain average size distribution. Generated 16S rRNA V3-V4 libraries were further quality-controlled using the following internal study criteria: 1. Library concentration of all negative(s) is < 5 ng/μl, 2. Participant samples have a fragment peak distribution with average size of ~ 600 bp, and 3. Negative controls yield a straight line when run in the Fragment Analyzer. If the above cutoffs were met, libraries were normalized and pooled to 4 nM based on PicoGreen concentrations. The pool of normalized libraries were then quantified with the NEBNext Library Quant Kit (New England Biolabs, Inc., Ipswich, M.), denatured with NaOH and diluted to a final concentration of 10 pM with a 20% PhiX (Illumina, Inc., San Diego, CA). 2 × 300 bp paired-end sequencing is performed in the Illumina MiSeq System (Illumina Inc., San Diego, CA) by multiplexing 96 samples per sequencing run with the MiSeq Reagent Kit.

Joining of Illumina paired-end reads were completed using Paired-End reAd mergeR (PEAR version 0.9.6). The percentage of successfully joined pair-end defined the “merge rate”; paired-end reads that could not be joined were removed from downstream analyses. Sequence quality filtering was done with the Fastx-Toolkit (V.0.013) to isolate reads with 90% of their bases having a score higher than Q30, which defined the “pass rate”; reads not meeting this criterion were removed. Primer sequences were trimmed based on the length of the forward and reverse sequencing primers. Following quality-filtering, reads were deduplicated by recording the number and type of identical sequences to reduce downstream processing time.

Taxonomy annotation was done with BLAST [31] at a 97% similarity, for species-level assignment approximation, against bacterial sequences from the HOMD version 14.5. Input query reads were given the same taxonomic label as the best hit in the reference sequence collection, defining the “hit count”; reads with no hits were excluded from downstream analyses. Sequences with the same labels were clustered into one OTU and the raw OTU table was constructed by combining absolute sequence abundances from the deduplication step, generated taxonomy annotations and manually generated metadata. We subsequently filtered the raw OTU table by discarding OTUs with a frequency < 0.02% of the total read count. At the preprocessing sequence analysis step we require a ‘Merge Rate’ ≥ 90%, ‘Pass Rate’ ≥ 60%, and ‘Hit Count’ per sample ≥ 3000.

Statistical analysis

For this analysis we used several approaches to characterize the composition and diversity of the subgingival microbiome and their relationships with age. Individual OTU counts were normalized using the centered log(2)-ratio (CLR) transformation. Gloor et al. [32] recommends the CLR transformation to account for the complex compositional data structure, to reduce the likelihood of spurious correlations, and to enhance the meaningfulness of subcomposition comparisons. A positive CLR OTU value for given taxon indicates a relatively higher amount than the overall composition mean, which is 0; a negative value indicates relatively lower amount. The fold-difference for a reported CLR OTU value relative to the compositional mean, can be determined by raising 2 to the power of the base 2 logarithm. For example, a mean CLR of 3, reflects an 8-fold (23) higher abundance compared to the compositional mean; a mean CLR of − 3 reflects an 8-fold lower abundance. The CLR distribution of each OTU was approximately normal and the variances in groups were similar by visual inspection. Alpha diversity was used to assess species richness and evenness across age categories. The rarefaction curve, bias-corrected Chao1 (richness), OTU count (richness), and Shannon entropy (evenness) values were calculated for each sample using scikit- bio v0.5.5. Beta diversity was evaluated using principal component analysis (PCA) [33]. T-tests were used to evaluate differences in alpha diversity, and PERMANOVA was used to evaluate differences in beta diversity, using SciPy v1.3.0. Comparisons of microbiota between age categories was performed using analysis of variance and evaluation of linear relationships between microbiota and age performed using Pearson product-moment correlations. We nominally defined correlations of |r| < 0.10 as weak, 0.10–0.49 as moderate, 0.50–0.70 as strong, and > 0.70 as very strong. We report uncorrected p-values and indicate which are statistically significant after Bonferroni correction for multiple testing.

To provide additional perspective and comparability with previous studies, we also describe microbiome composition and diversity according to conventional measures of relative abundance (the amount of a specific taxon relative to the total composition of the sample in which it is measured) and prevalence (presence of a taxon regardless of relative composition). To minimize the total number of hypothesis tests performed, formal comparisons using these measures were not conducted and these data are presented for descriptive purposes only.

Results

Characteristics of study group

Participant characteristics are shown for descriptive purposes in Table 1. Women in the present study were, on average, 66 years of age and the vast majority (97%) were Caucasian. Prevalence of current smoking (3%) and diabetes history (5.2%) was modest, and about half the group reported current use of hormone therapy. The group retained the majority of their natural teeth (mean, 23), the frequency of reported teeth brushing two or more times per day was high (77%) as was frequency of dental visits one or more times per year (91%). Mean pocket depth was 2.2 mm (range 1.2–3.8). As expected, prevalence of current smoking and current hormone therapy use declined with increasing age, and, prevalence of diabetes history was highest among the oldest women. The number of teeth present and frequency of dental visits declined with increasing age and, frequency of teeth brushing was higher in older than younger women. Both neighborhood socioeconomic status and mean pocket depth were similar across age groups.
Table 1

Baseline characteristics of OsteoPerio Microbiome Study participants for the overall cohort and by age groups

Characteristic

Overall

(N = 1219)

50–59

(N = 239)

60–69

(N = 554)

≥70

(N = 426)

Age (years), mean (SD)

66.2 (7.0)

56.7 (1.8)

64.2 (2.9)

74.1 (3.3)

Race-ethnicity: White, N (%)

1187 (97.4)

233 (97.5)

537 (96.9)

417 (97.9)

Neighborhood SES, mean (SD)

76.2 (6.9)

75.7 (7.5)

76.6 (6.8)

75.9 (6.7)

Smoking, N (%)

 Never

642 (52.7)

117 (48.9)

280 (50.5)

245 (57.6)

 Former

537 (44.1)

107 (44.8)

257 (46.4)

173 (40.7)

 Current

39 (3.2)

15 (6.3)

17 (3.1)

7 (1.7)

History of treated diabetes, N (%)

63 (5.2)

9 (3.8)

26 (4.7)

28 (6.6)

History of treated hypertension, N (%)

392 (32.2)

63 (26.4)

148 (26.7)

181 (42.5)

History of treated high cholesterol, N (%)

201 (16.5)

26 (10.9)

76 (13.7)

99 (23.4)

Hormone therapy use, N (%)

 Never

390 (32.0)

53 (22.2)

158 (28.5)

179 (42.0)

 Former E-Alone

132 (10.9)

12 (5.0)

50 (9.0)

70 (16.5)

 Former E + P

111 (9.1)

24 (10.1)

58 (10.5)

29 (6.8)

 Current E-Alone

307 (25.2)

66 (27.7)

136 (24.6)

105 (24.7)

 Current E + P

277 (22.8)

83 (34.9)

152 (27.4)

42 (9.9)

 Years taking hormone therapya

5.6 (7.3)

4.6 (4.5)

6.2 (7.0)

5.5 (8.8)

Number of teeth present, mean (SD)

23.2 (5.3)

24.8 (4.0)

23.6 (5.2)

21.9 (5.8)

Brush teeth ≥2 times/day, N (%)

942 (77.3)

178 (74.5)

422 (76.2)

342 (80.3)

Floss teeth daily, N (%)

529 (43.6)

90 (37.7)

247 (44.8)

192 (45.4)

Dental visit ≥1 time/year, N (%)

1114 (91.4)

225 (94.1)

504 (91.0)

385 (90.4)

Mean Pocket Depth (mm), mean (SD)

2.2 (0.4)

2.2 (0.4)

2.2 (0.4)

2.1 (0.4)

Gingival Bleeding (%), mean (SD)

34.4 (23.2)

33.0 (23.5)

34.5 (22.9)

35.1 (23.4)

SES socioeconomic statusn. See methods section for its definition and derivation, E estrogen, P progesti

aNever users coded as 0 years

Microbial community structure and composition

After filtering out OTUs < 0.02%, the total number of sequence reads for the overall cohort of 1219 women was 120,388,085 (mean reads per sample, 98,760; range 3034 to 1,080,317). Sequence reads per sample was somewhat higher with increasing age, with means (SDs) of 89,442 (71,698), 97,794 (86,908), and 105,243 (80,183) reads in women ages 50–59, 60–69, and ≥ 70 years, respectively. There were 267 microbial taxa identified in the subgingival plaque samples after filtering at 0.02%. The taxonomic classification and mean reads for each taxon overall and by age groups, are presented in Table 2. Of the 120,388,085 read, 46.2% were of the phylum Firmicutes, 17.2% Bacteroidetes, 13.5% Fusobacterium, 8.6% Proteobacteria, 6.0% Actinobacteria, and the remaining were among other phyla of < 4%, each (Fig. 2). The distribution of phyla was consistent across age groups. At the genus level, the highest mean relative abundance was for Veillonella (16.7%), followed by Streptococcus (14.2%), Fusobacterium (10.7%), Prevotella (8.6%), and Selenomonas (7.7%); relative abundance of the remaining genera was < 4%, each. This pattern was consistent across age groups. At the species level, among all women, the highest number of mean reads was for Veillonella dispar (Firmicutes phylum; mean, 8136) and Veillonella parvula (Firmicutes phylum; mean, 6262) (Table 2). Mean reads for each taxon increased across incremental age groups.
Table 2

Taxonomic classification and mean reads for the 267 bacteria identified, overall and by age groups

Phyla

Class

Genus

Species

 

Age Categories (years)

Overall

50–59

60–69

≥70

p__Actinobacteria

c__Actinobacteria

g__Actinobaculum

s__sp._oral_taxon_183

89.8

95.0

88.9

88.0

p__Actinobacteria

c__Actinobacteria

g__Actinobaculum

s__sp._oral_taxon_848

48.2

37.3

52.9

48.2

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__gerencseriae

68.6

60.5

66.7

75.6

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__israelii

25.1

19.5

24.1

29.5

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__johnsonii

106.0

104.9

105.2

107.6

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__massiliensis

112.1

134.2

121.5

87.4

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__meyeri

59.3

64.8

61.6

53.3

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__naeslundii

453.1

482.6

447.6

443.6

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__oris

225.7

236.6

218.8

228.5

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__sp._oral_taxon_169

195.8

251.2

183.7

180.4

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__sp._oral_taxon_170

60.4

44.8

59.8

70.0

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__sp._oral_taxon_171

88.2

86.5

89.2

87.9

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__sp._oral_taxon_178

27.0

23.9

26.8

29.0

p__Actinobacteria

c__Actinobacteria

g__Actinomyces

s__sp._oral_taxon_180

119.0

121.7

123.6

111.5

p__Actinobacteria

c__Actinobacteria

g__Bifidobacterium

s__dentium

88.5

83.0

75.8

108.2

p__Actinobacteria

c__Actinobacteria

g__Corynebacterium

s__durum

121.3

153.3

120.2

104.7

p__Actinobacteria

c__Actinobacteria

g__Corynebacterium

s__matruchotii

1107

1095

1178

1020

p__Actinobacteria

c__Actinobacteria

g__Microbacterium

s__flavescens

1.5

1.8

1.6

1.1

p__Actinobacteria

c__Actinobacteria

g__Rothia

s__aeria

323.3

311.6

378.9

257.6

p__Actinobacteria

c__Actinobacteria

g__Rothia

s__dentocariosa

975.6

915.0

1039

927.8

p__Actinobacteria

c__Actinobacteria

g__Rothia

s__mucilaginosa

185.3

125.4

179.1

226.9

p__Actinobacteria

c__Actinobacteria

g__Scardovia

s__wiggsiae

68.7

74.1

69.7

64.4

p__Actinobacteria

c__Coriobacteriia

g__Atopobium

s__parvulum

77.9

57.2

78.3

88.8

p__Actinobacteria

c__Coriobacteriia

g__Atopobium

s__rimae

200.0

107.8

200.0

251.7

p__Actinobacteria

c__Coriobacteriia

g__Atopobium

s__sp._oral_taxon_199

47.4

39.1

61.2

34.0

p__Actinobacteria

c__Coriobacteriia

g__Atopobium

s__sp._oral_taxon_416

25.4

1.1

14.6

53.1

p__Actinobacteria

c__Coriobacteriia

g__Olsenella

s__sp._oral_taxon_807

46.9

38.6

44.5

54.7

p__Bacteroidetes

c__Bacteroidetes_[C-1]

g__Bacteroidetes_[G-5]

s__sp._oral_taxon_511

137.4

87.8

155.7

141.4

p__Bacteroidetes

c__Bacteroidia

g__Alloprevotella

s__rava

82.4

52.8

87.6

92.3

p__Bacteroidetes

c__Bacteroidia

g__Alloprevotella

s__sp._oral_taxon_308

28.6

21.3

24.9

37.4

p__Bacteroidetes

c__Bacteroidia

g__Alloprevotella

s__sp._oral_taxon_473

77.5

63.0

82.6

79.1

p__Bacteroidetes

c__Bacteroidia

g__Alloprevotella

s__tannerae

1562

1427

1580

1615

p__Bacteroidetes

c__Bacteroidia

g__Bacteroidaceae_[G-1]

s__sp._oral_taxon_272

39.5

24.6

28.6

62.2

p__Bacteroidetes

c__Bacteroidia

g__Bacteroidales_[G-2]

s__sp._oral_taxon_274

885.8

548.7

935.5

1010

p__Bacteroidetes

c__Bacteroidia

g__Porphyromonas

s__catoniae

104.1

111.4

115.8

84.7

p__Bacteroidetes

c__Bacteroidia

g__Porphyromonas

s__endodontalis

602.5

560.5

657.1

555.0

p__Bacteroidetes

c__Bacteroidia

g__Porphyromonas

s__gingivalis

1055

781.4

752.8

1603

p__Bacteroidetes

c__Bacteroidia

g__Porphyromonas

s__sp._oral_taxon_275

46.0

29.0

62.6

33.9

p__Bacteroidetes

c__Bacteroidia

g__Porphyromonas

s__sp._oral_taxon_278

39.2

22.1

43.1

43.6

p__Bacteroidetes

c__Bacteroidia

g__Porphyromonas

s__sp._oral_taxon_279

310.5

255.9

315.5

334.7

p__Bacteroidetes

c__Bacteroidia

g__Porphyromonas

s__sp._oral_taxon_284

183.2

187.5

187.8

174.9

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__baroniae

50.3

29.2

60.5

48.8

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__buccae

53.1

17.3

63.0

60.4

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__dentalis

102.3

63.3

120.3

100.8

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__denticola

773.5

501.4

724.4

989.9

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__histicola

100.3

48.8

72.7

165.3

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__intermedia

671.5

613.0

766.5

580.8

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__loescheii

119.6

131.7

138.7

87.8

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__maculosa

185.9

139.8

180.0

219.4

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__melaninogenica

339.1

236.0

321.8

419.4

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__micans

42.7

37.6

37.1

52.9

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__multiformis

46.7

9.2

36.1

81.6

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__nigrescens

1997

1719

1960

2200

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__oralis

174.4

78.8

158.9

248.2

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__oris

1968

1700

2093

1956

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__oulorum

211.7

216.2

182.8

246.8

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__pallens

94.4

91.5

71.4

125.9

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__pleuritidis

579.6

478.7

606.4

601.4

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__saccharolytica

73.7

52.8

80.9

76.1

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__salivae

120.5

94.7

117.3

139.1

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_292

69.4

50.1

57.5

95.7

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_300

269.5

256.3

243.5

310.7

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_306

41.1

17.2

38.9

57.5

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_313

70.5

86.9

44.0

95.8

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_314

65.2

59.2

52.7

85.0

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_317

832.0

631.4

832.4

944.0

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_376

44.8

45.1

43.6

46.1

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_472

250.3

270.4

279.0

201.9

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_475

21.8

19.1

17.4

28.9

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__sp._oral_taxon_526

55.1

21.5

70.7

53.7

p__Bacteroidetes

c__Bacteroidia

g__Prevotella

s__veroralis

113.8

84.1

160.3

70.0

p__Bacteroidetes

c__Bacteroidia

g__Tannerella

s__forsythia

577.6

374.7

542.0

737.8

p__Bacteroidetes

c__Bacteroidia

g__Tannerella

s__sp._oral_taxon_286

93.0

68.6

100.9

96.6

p__Bacteroidetes

c__Bacteroidia

g__Tannerella

s__sp._oral_taxon_808

35.6

25.4

32.6

45.3

p__Bacteroidetes

c__Flavobacteriia

g__Bergeyella

s__sp._oral_taxon_322

164.1

194.8

173.9

134.1

p__Bacteroidetes

c__Flavobacteriia

g__Bergeyella

s__sp._oral_taxon_907

34.8

34.7

36.7

32.4

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__gingivalis

502.9

619.2

471.7

478.3

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__granulosa

597.4

513.3

629.6

602.6

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__leadbetteri

614.5

534.6

619.4

653.0

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_323

37.7

26.7

40.2

40.5

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_324

33.8

19.5

32.3

43.8

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_326

258.0

222.7

281.8

246.9

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_332

64.5

104.3

60.6

47.3

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_336

159.5

127.8

157.8

179.6

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_338

62.3

62.5

56.7

69.5

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_380

29.6

23.3

40.3

19.1

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_412

43.7

42.0

46.4

41.2

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_864

76.3

76.5

80.4

70.9

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_902

45.4

51.0

43.5

44.7

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sp._oral_taxon_903

37.1

26.6

37.4

42.5

p__Bacteroidetes

c__Flavobacteriia

g__Capnocytophaga

s__sputigena

416.4

448.8

405.0

413.0

p__Chloroflexi

c__Anaerolineae

g__Anaerolineae_[G-1]

s__sp._oral_taxon_439

59.1

30.1

54.2

81.8

p__Firmicutes

c__Bacilli

g__Abiotrophia

s__defectiva

104.2

135.7

109.9

79.0

p__Firmicutes

c__Bacilli

g__Gemella

s__haemolysans

338.8

412.1

338.9

297.4

p__Firmicutes

c__Bacilli

g__Gemella

s__morbillorum

603.8

670.7

622.2

542.2

p__Firmicutes

c__Bacilli

g__Gemella

s__sanguinis

44.3

33.8

36.2

60.7

p__Firmicutes

c__Bacilli

g__Granulicatella

s__adiacens

532.6

564.2

523.2

527.1

p__Firmicutes

c__Bacilli

g__Granulicatella

s__elegans

39.7

49.7

37.7

36.7

p__Firmicutes

c__Bacilli

g__Lactobacillus

s__gasseri

31.4

9.3

37.7

35.5

p__Firmicutes

c__Bacilli

g__Streptococcus

s__anginosus

479.8

409.3

468.1

534.6

p__Firmicutes

c__Bacilli

g__Streptococcus

s__australis

28.9

21.0

24.1

39.5

p__Firmicutes

c__Bacilli

g__Streptococcus

s__constellatus

283.7

208.0

279.1

332.2

p__Firmicutes

c__Bacilli

g__Streptococcus

s__cristatus

516.2

457.7

546.4

509.7

p__Firmicutes

c__Bacilli

g__Streptococcus

s__gordonii

998.1

853.8

991.3

1088

p__Firmicutes

c__Bacilli

g__Streptococcus

s__intermedius

897.1

1038

949.4

749.9

p__Firmicutes

c__Bacilli

g__Streptococcus

s__lactarius

56.8

97.9

40.2

55.3

p__Firmicutes

c__Bacilli

g__Streptococcus

s__mutans

530.8

392.2

500.4

648.0

p__Firmicutes

c__Bacilli

g__Streptococcus

s__oralis

6725

8031

6651

6089

p__Firmicutes

c__Bacilli

g__Streptococcus

s__parasanguinis_I

59.7

48.6

51.2

77.0

p__Firmicutes

c__Bacilli

g__Streptococcus

s__parasanguinis_II

141.3

124.2

126.4

170.2

p__Firmicutes

c__Bacilli

g__Streptococcus

s__salivarius

460.0

399.7

455.1

500.2

p__Firmicutes

c__Bacilli

g__Streptococcus

s__sanguinis

1128

1441

1133

945.5

p__Firmicutes

c__Bacilli

g__Streptococcus

s__sinensis

29.3

32.1

14.3

47.4

p__Firmicutes

c__Bacilli

g__Streptococcus

s__sobrinus

52.0

2.5

19.9

121.7

p__Firmicutes

c__Bacilli

g__Streptococcus

s__sp._oral_taxon_056

90.0

102.7

82.4

92.7

p__Firmicutes

c__Bacilli

g__Streptococcus

s__sp._oral_taxon_074

68.3

54.3

71.9

71.6

p__Firmicutes

c__Clostridia

g__Butyrivibrio

s__sp._oral_taxon_080

24.6

14.1

35.9

15.9

p__Firmicutes

c__Clostridia

g__Catonella

s__morbi

230.1

228.9

222.5

240.8

p__Firmicutes

c__Clostridia

g__Filifactor

s__alocis

368.2

274.3

418.9

355.0

p__Firmicutes

c__Clostridia

g__Johnsonella

s__ignava

114.9

104.7

111.8

124.5

p__Firmicutes

c__Clostridia

g__Johnsonella

s__sp._oral_taxon_166

32.7

17.7

43.8

26.7

p__Firmicutes

c__Clostridia

g__Lachnoanaerobaculum

s__orale

31.4

35.3

24.9

37.6

p__Firmicutes

c__Clostridia

g__Lachnoanaerobaculum

s__saburreum

152.3

124.4

153.0

167.0

p__Firmicutes

c__Clostridia

g__Lachnoanaerobaculum

s__umeaense

52.9

50.6

55.5

50.7

p__Firmicutes

c__Clostridia

g__Lachnospiraceae_[G-3]

s__sp._oral_taxon_100

132.2

118.4

143.0

125.9

p__Firmicutes

c__Clostridia

g__Lachnospiraceae_[G-8]

s__sp._oral_taxon_500

45.1

40.6

48.1

43.7

p__Firmicutes

c__Clostridia

g__Oribacterium

s__sp._oral_taxon_078

112.2

68.2

102.9

149.0

p__Firmicutes

c__Clostridia

g__Parvimonas

s__micra

848.4

791.4

915.0

793.8

p__Firmicutes

c__Clostridia

g__Parvimonas

s__sp._oral_taxon_393

265.1

361.3

250.6

230.0

p__Firmicutes

c__Clostridia

g__Peptostreptococcaceae_[XI][G-1]

s__[Eubacterium]_infirmum

38.9

32.2

32.2

51.2

p__Firmicutes

c__Clostridia

g__Peptostreptococcaceae_[XI][G-5]

s__[Eubacterium]_saphenum

87.3

55.6

107.1

79.2

p__Firmicutes

c__Clostridia

g__Peptostreptococcaceae_[XI][G-6]

s__[Eubacterium]_nodatum

64.3

60.2

55.8

77.7

p__Firmicutes

c__Clostridia

g__Peptostreptococcaceae_[XI][G-7]

s__[Eubacterium]_yurii_subsps._yur

146.2

167.1

151.3

127.9

p__Firmicutes

c__Clostridia

g__Peptostreptococcaceae_[XI][G-9]

s__[Eubacterium]_brachy

200.8

208.5

203.6

192.7

p__Firmicutes

c__Clostridia

g__Peptostreptococcus

s__stomatis

107.9

130.7

103.5

100.7

p__Firmicutes

c__Clostridia

g__Pseudoramibacter

s__alactolyticus

70.8

73.3

52.7

93.0

p__Firmicutes

c__Clostridia

g__Ruminococcaceae_[G-1]

s__sp._oral_taxon_075

83.8

109.4

79.6

74.9

p__Firmicutes

c__Clostridia

g__Shuttleworthia

s__satelles

35.3

21.3

40.5

36.3

p__Firmicutes

c__Clostridia

g__Stomatobaculum

s__longum

55.2

47.4

52.5

63.0

p__Firmicutes

c__Erysipelotrichia

g__Solobacterium

s__moorei

42.1

40.4

41.0

44.6

p__Firmicutes

c__Mollicutes

g__Mycoplasma

s__salivarium

33.0

24.9

30.9

40.4

p__Firmicutes

c__Negativicutes

g__Anaeroglobus

s__geminatus

767.6

402.1

582.4

1214

p__Firmicutes

c__Negativicutes

g__Centipeda

s__periodontii

93.0

45.3

106.0

102.9

p__Firmicutes

c__Negativicutes

g__Dialister

s__invisus

612.2

466.3

625.5

676.8

p__Firmicutes

c__Negativicutes

g__Dialister

s__pneumosintes

225.5

179.8

224.8

252.1

p__Firmicutes

c__Negativicutes

g__Megasphaera

s__micronuciformis

208.0

136.7

212.5

242.2

p__Firmicutes

c__Negativicutes

g__Megasphaera

s__sp._oral_taxon_123

158.7

166.4

138.4

180.8

p__Firmicutes

c__Negativicutes

g__Mitsuokella

s__sp._oral_taxon_131

117.5

40.4

143.3

127.2

p__Firmicutes

c__Negativicutes

g__Mitsuokella

s__sp._oral_taxon_521

31.2

11.1

13.3

65.7

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__artemidis

738.5

720.4

712.4

782.7

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__dianae

47.4

36.6

36.3

67.9

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__flueggei

166.3

137.2

160.7

190.0

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__infelix

272.6

194.0

268.0

322.7

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__noxia

1502

1474

1514

1500

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_126

102.4

92.1

105.4

104.2

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_133

44.7

44.7

43.4

46.3

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_134

357.6

200.4

361.3

440.9

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_136

318.2

182.9

317.6

394.8

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_137

494.2

423.6

520.8

499.2

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_146

119.4

98.3

117.8

133.2

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_149

19.7

9.7

25.0

18.4

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_442

27.3

14.0

37.6

21.3

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_478

15.5

12.0

12.6

21.2

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_892

223.3

222.2

211.7

239.0

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_919

187.4

170.1

178.5

208.7

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_936

83.7

62.0

73.5

109.1

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sp._oral_taxon_937

22.1

14.6

22.5

25.7

p__Firmicutes

c__Negativicutes

g__Selenomonas

s__sputigena

3283

2195

2957

4319

p__Firmicutes

c__Negativicutes

g__Veillonella

s__atypica

586.0

380.8

569.5

722.5

p__Firmicutes

c__Negativicutes

g__Veillonella

s__denticariosi

201.2

265.6

159.9

218.6

p__Firmicutes

c__Negativicutes

g__Veillonella

s__dispar

8720

7556

8534

9615

p__Firmicutes

c__Negativicutes

g__Veillonella

s__parvula

6529

5964

6121

7376

p__Firmicutes

c__Negativicutes

g__Veillonella

s__rogosae

202.3

138.4

208.0

230.9

p__Firmicutes

c__Negativicutes

g__Veillonella

s__sp._oral_taxon_780

109.3

147.1

100.8

99.2

p__Firmicutes

c__Negativicutes

g__Veillonellaceae_[G-1]

s__sp._oral_taxon_129

54.4

27.0

45.9

81.0

p__Firmicutes

c__Negativicutes

g__Veillonellaceae_[G-1]

s__sp._oral_taxon_145

59.1

39.5

58.4

70.9

p__Firmicutes

c__Negativicutes

g__Veillonellaceae_[G-1]

s__sp._oral_taxon_150

295.0

204.8

251.6

402.1

p__Firmicutes

c__Negativicutes

g__Veillonellaceae_[G-1]

s__sp._oral_taxon_155

265.6

194.6

212.4

374.6

p__Fusobacteria

c__Fusobacteriia

g__Fusobacterium

s__naviforme

826.5

725.4

813.9

899.6

p__Fusobacteria

c__Fusobacteriia

g__Fusobacterium

s__nucleatum_subsp._animalis

1650

1387

1575

1896

p__Fusobacteria

c__Fusobacteriia

g__Fusobacterium

s__nucleatum_subsp._nucleatum

223.2

165.8

149.4

351.4

p__Fusobacteria

c__Fusobacteriia

g__Fusobacterium

s__nucleatum_subsp._polymorphum

1439

1467

1499

1345

p__Fusobacteria

c__Fusobacteriia

g__Fusobacterium

s__nucleatum_subsp._vincentii

3930

3647

3798

4262

p__Fusobacteria

c__Fusobacteriia

g__Fusobacterium

s__periodonticum

87.3

57.2

88.7

102.2

p__Fusobacteria

c__Fusobacteriia

g__Fusobacterium

s__sp._oral_taxon_203

1968

1576

2223

1857

p__Fusobacteria

c__Fusobacteriia

g__Fusobacterium

s__sp._oral_taxon_370

34.1

36.1

37.0

29.2

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__buccalis

399.0

365.5

436.8

368.7

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__goodfellowii

22.9

26.0

24.7

18.7

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__hofstadii

346.7

418.6

364.3

283.4

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__hongkongensis

388.3

297.8

360.4

475.3

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__shahii

387.0

312.2

250.1

607.1

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_212

253.4

237.4

264.5

248.1

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_215

107.2

117.0

107.5

101.2

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_219

36.9

37.3

35.4

38.6

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_223

78.4

39.0

82.6

95.1

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_225

244.7

299.5

328.2

105.5

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_392

195.9

187.9

212.8

178.3

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_417

363.2

241.0

408.8

372.5

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_498

210.4

135.1

176.6

296.4

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__sp._oral_taxon_879

52.3

57.8

31.4

76.5

p__Fusobacteria

c__Fusobacteriia

g__Leptotrichia

s__wadei

767.1

783.8

675.4

877.0

p__Gracilibacteria_(GN02)

c__GN02_[C-2]

g__GN02_[G-2]

s__sp._oral_taxon_873

24.8

31.7

18.7

29.0

p__Proteobacteria

c__Alphaproteobacteria

g__Bradyrhizobium

s__elkanii

31.9

36.6

31.5

29.8

p__Proteobacteria

c__Alphaproteobacteria

g__Brevundimonas

s__diminuta

0.6

0.9

0.5

0.6

p__Proteobacteria

c__Alphaproteobacteria

g__Porphyrobacter

s__tepidarius

0.2

0.1

0.1

0.3

p__Proteobacteria

c__Alphaproteobacteria

g__Sphingomonas

s__echinoides

9.2

8.0

9.3

9.7

p__Proteobacteria

c__Alphaproteobacteria

g__Sphingomonas

s__sp._oral_taxon_006

0.5

0.3

0.2

1.1

p__Proteobacteria

c__Betaproteobacteria

g__Eikenella

s__corrodens

264.4

284.9

279.0

233.9

p__Proteobacteria

c__Betaproteobacteria

g__Kingella

s__denitrificans

159.5

149.8

146.3

182.3

p__Proteobacteria

c__Betaproteobacteria

g__Kingella

s__oralis

311.9

324.2

285.2

339.8

p__Proteobacteria

c__Betaproteobacteria

g__Lautropia

s__mirabilis

145.1

173.9

144.3

129.9

p__Proteobacteria

c__Betaproteobacteria

g__Leptothrix

s__sp._oral_taxon_025

0.3

0.6

0.4

0.2

p__Proteobacteria

c__Betaproteobacteria

g__Neisseria

s__bacilliformis

84.2

70.1

80.2

97.4

p__Proteobacteria

c__Betaproteobacteria

g__Neisseria

s__elongata

499.3

682.7

506.5

387.0

p__Proteobacteria

c__Betaproteobacteria

g__Neisseria

s__flavescens

440.2

302.3

352.9

631.0

p__Proteobacteria

c__Betaproteobacteria

g__Neisseria

s__oralis

376.2

558.0

272.4

409.2

p__Proteobacteria

c__Betaproteobacteria

g__Neisseria

s__pharyngis

70.1

86.1

41.5

98.3

p__Proteobacteria

c__Betaproteobacteria

g__Neisseria

s__sicca

730.6

656.1

784.9

701.7

p__Proteobacteria

c__Betaproteobacteria

g__Neisseria

s__subflava

174.1

125.9

194.7

174.4

p__Proteobacteria

c__Betaproteobacteria

g__Ottowia

s__sp._oral_taxon_894

70.0

88.8

70.2

59.3

p__Proteobacteria

c__Deltaproteobacteria

g__Desulfobulbus

s__sp._oral_taxon_041

139.1

91.1

132.8

174.4

p__Proteobacteria

c__Epsilonproteobacteria

g__Campylobacter

s__concisus

242.1

186.5

241.4

274.2

p__Proteobacteria

c__Epsilonproteobacteria

g__Campylobacter

s__curvus

39.6

46.6

31.6

46.1

p__Proteobacteria

c__Epsilonproteobacteria

g__Campylobacter

s__gracilis

858.3

734.1

849.7

939.1

p__Proteobacteria

c__Epsilonproteobacteria

g__Campylobacter

s__showae

496.9

422.2

521.4

507.0

p__Proteobacteria

c__Gammaproteobacteria

g__Aggregatibacter

s__actinomycetemcomitans

49.2

68.1

46.4

42.2

p__Proteobacteria

c__Gammaproteobacteria

g__Aggregatibacter

s__aphrophilus

312.9

232.7

392.3

254.5

p__Proteobacteria

c__Gammaproteobacteria

g__Aggregatibacter

s__paraphrophilus

111.5

126.7

141.8

63.6

p__Proteobacteria

c__Gammaproteobacteria

g__Aggregatibacter

s__segnis

233.8

295.3

259.7

165.6

p__Proteobacteria

c__Gammaproteobacteria

g__Aggregatibacter

s__sp._oral_taxon_458

158.1

130.8

151.6

181.8

p__Proteobacteria

c__Gammaproteobacteria

g__Aggregatibacter

s__sp._oral_taxon_513

61.5

35.1

85.1

45.7

p__Proteobacteria

c__Gammaproteobacteria

g__Cardiobacterium

s__hominis

277.9

342.4

295.3

219.1

p__Proteobacteria

c__Gammaproteobacteria

g__Cardiobacterium

s__valvarum

234.5

257.9

245.6

207.0

p__Proteobacteria

c__Gammaproteobacteria

g__Haemophilus

s__haemolyticus

50.2

95.7

34.4

45.4

p__Proteobacteria

c__Gammaproteobacteria

g__Haemophilus

s__parahaemolyticus

78.5

71.7

121.9

26.0

p__Proteobacteria

c__Gammaproteobacteria

g__Haemophilus

s__parainfluenzae

1042

1480

940.9

927.4

p__Proteobacteria

c__Gammaproteobacteria

g__Haemophilus

s__sp._oral_taxon_036

75.0

82.2

71.0

76.2

p__Proteobacteria

c__Gammaproteobacteria

g__Pseudomonas

s__fluorescens

52.5

52.2

53.4

51.6

p__SR1

c__SR1_[C-1]

g__SR1_[G-1]

s__sp._oral_taxon_874

26.9

26.4

29.2

24.3

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-1]

s__sp._oral_taxon_346

1103

901.9

1098

1223

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-1]

s__sp._oral_taxon_347

100.0

143.7

105.6

68.1

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-1]

s__sp._oral_taxon_348

106.9

75.8

123.5

102.9

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-1]

s__sp._oral_taxon_349

1107

900.9

1062

1279

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-1]

s__sp._oral_taxon_352

49.4

42.8

43.6

60.5

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-1]

s__sp._oral_taxon_488

136.2

146.7

156.0

104.4

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-1]

s__sp._oral_taxon_869

125.1

120.6

128.5

123.1

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-1]

s__sp._oral_taxon_952

665.5

706.5

669.6

637.1

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-2]

s__sp._oral_taxon_350

156.1

137.7

139.2

188.3

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-3]

s__sp._oral_taxon_351

33.2

21.1

35.6

36.9

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-5]

s__sp._oral_taxon_356

616.8

371.0

677.8

675.5

p__Saccharibacteria_(TM7)

c__TM7_[C-1]

g__TM7_[G-6]

s__sp._oral_taxon_870

82.6

93.6

83.9

74.6

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__denticola

372.7

246.3

374.0

442.1

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__lecithinolyticum

65.5

62.1

65.8

67.0

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__maltophilum

83.6

56.0

73.1

112.7

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__medium

45.7

27.4

60.7

36.3

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__socranskii

297.0

211.8

294.6

348.0

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__sp._oral_taxon_231

102.7

75.9

117.3

98.6

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__sp._oral_taxon_237

160.6

104.6

160.5

192.0

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__sp._oral_taxon_247

44.0

8.2

68.9

31.7

p__Spirochaetes

c__Spirochaetia

g__Treponema

s__vincentii

27.6

36.1

33.3

15.4

p__Synergistetes

c__Synergistia

g__Fretibacterium

s__fastidiosum

551.9

462.9

595.3

545.5

p__Synergistetes

c__Synergistia

g__Fretibacterium

s__sp._oral_taxon_358

81.3

46.0

93.4

85.3

p__Synergistetes

c__Synergistia

g__Fretibacterium

s__sp._oral_taxon_359

722.3

648.0

814.1

644.6

p__Synergistetes

c__Synergistia

g__Fretibacterium

s__sp._oral_taxon_360

1247

818.0

1325

1385

p__Synergistetes

c__Synergistia

g__Fretibacterium

s__sp._oral_taxon_361

54.1

4.5

61.8

71.9

p__Synergistetes

c__Synergistia

g__Fretibacterium

s__sp._oral_taxon_362

212.8

161.8

233.9

213.9

p__Synergistetes

c__Synergistia

g__Pyramidobacter

s__piscolens

5.7

7.9

4.6

5.9

Fig. 2

Distribution of phyla among the total reads identified, overall and according to categories of age. Numbers on chart are mean relative abundance. The “other” phylum category comprises 5 phyla ranging in frequency from 0.02 to 3.9%

For three known highly virulent periodontal pathogens, Porphyromonas ginigivalis (Bacteroidetes phylum), Tannerella forsythia (Bacteroidetes phylum), and Treponema denticola (Spirochaetes phylum), overall mean reads were 1055, 577.6, and 372.7, respectively; mean reads for each increased with age. Mean reads for bacteria typically associated with periodontal health (Streptococcus oralis, sanguinis and intermedius; Firmicutes phylum) were 6725, 1128, and 897; each decreasing across incremental age groups. To further evaluate the distribution of the two predominant phyla, we computed the Firmicutes-to-Bacteroidetes ratio by summing the mean reads separately within each of these phyla (Table 2) and then creating a ratio of these sums. The ratio was 1.56 among all women, and increased with age: 1.45 (50–69 years); 1.55 (60–69 years); and 1.61 (≥70 years).

We next evaluated alpha (within-group) and beta (between-group) diversity of the bacterial species in the overall cohort and according to age categories. For alpha (within-group) diversity, mean (SD), OTU count richness, Chao1 richness, and Shannon entropy evenness were 165 (45.1), 185.0 (31.2), and 5.0 (0.7), respectively, among all women, and remained consistent across age categories (Fig. 3). Beta (between-group) diversity is shown in the PCA plot in Fig. 4. A Permutation MANOVA test yielded P = 0.001, suggesting that differences were present in mean vectors across age categories, despite unclear clustering in the PCA plot itself.
Fig. 3

Alpha (within-group) diversity of identified taxa according to age groups. Panel a gives the rarefaction curve and Panel b gives measures of richness (Chao-1, P = 0.55; OTU counts, P = 0.35) and evenness (Shannon entropy, P = 0.42)

Fig. 4

Beta (between-group) diversity of identified taxa according to age groups. Permutation MANOVA test yielded P = 0.001, suggesting differences are present in mean vectors (triangles) across age categories, despite unclear clustering in the PCA plot

Table 3 presents the top 20 highest and top 20 lowest OTUs based on their CLR mean for the overall cohort and according to age categories. Also shown in Table 3 are linear correlations between these OTUs and age, as well as an indication of whether or not the OTU has previously been cultured and named in the HOMD, and a notation of membership within the Socransky color complex of bacterial species previously identified using targeted methods [34]. Veillonella dispar (CLR mean, 8.3), S. Oralis (CLR mean 8.1), and Veillonella parvula (CLR mean, 7.6) had the greatest abundance, about a 256-fold (28) higher than the overall composition mean. There were 18 (90%) taxa with a 16-fold or greater (CLR mean ≥ 4) elevation in abundance based on CLR mean OTUs. Among the top 20 most abundant bacteria, 19 (95%) were previously named, whereas one (5%) was previously unnamed in HOMD. Among the top 20 taxa were bacteria previously associated with both periodontal health (S. oralis, sanguinis, gordonii, and intermedius) and periodontal disease (V. parvula; Fusobacterium nucleatum; Parvomonas micra; Prevotella nigrescens; Rothia dentocariosa; Actinomyces naeslundii). Ten of the top 20 bacteria were included in Socransky’s complex organization, with four (20%) from the yellow complex typically associated with healthy periodontium and four (20%) from the orange complex which is associated with periodontitis. Among taxa with reduced abundance, Porphyrobacter tepidarius (CLR mean, − 3.6), Sphingomonas sp._oral_taxon 006 (CLR mean, − 3.6), Pyramidobacter piscolens (CLR mean, − 3.5), Leptothirix sp._oral_taxon 025 (CLR mean, − 3.5), and Treponema sp._oral_taxon 247 (CLR mean, − 3.5) each had a 11-fold or lower abundance relative to the overall composition mean. Seven (35%) of the 20 least abundant bacteria have been previously named in HOMD; two (10%) are unnamed; and, 11 (55%) have been phylotyped, but as yet not named.
Table 3

Top 20 highest* and lowest* mean CLR OTU for the overall cohort and by age categories, and their linear correlation with age

Rank Order*

OTU Label

Culture Status

Socransky Complex

Overall Cohort (N = 1219)

Age Categories (years)

Linear Correlation

     

50–59 (N = 239)

60–69 (N = 554)

≥70 (N = 426)

p-value

Pearson r

p-value

CLR OTU

Mean (SE)

CLR OTU

Mean (SE)

CLR OTU

Mean (SE)

CLR OTU

Mean (SE)

20 Most Abundant Species

 1

Veillonella dispar

N

8.25 (0.06)

8.23 (0.13)

8.11 (0.09)

8.45 (0.10)

0.045

0.08

0.008

 2

Streptococcus oralis

N

Y

8.06 (0.05)

8.40 (0.11)

8.06 (0.08)

7.87 (0.09)

0.002

−0.10

<.001

 3

Veillonella parvula

N

P

7.60 (0.07)

7.48 (0.15)

7.45 (0.09)

7.86 (0.11)

0.014

0.10

0.001

 4

Fusobacterium nucleatum_subsp._vincentii

N

O

6.43 (0.08)

6.21 (0.17)

6.48 (0.11)

6.50 (0.13)

0.356

0.02

0.587

 5

Selenomonas sputigena

N

5.63 (0.08)

5.34 (0.17)

5.44 (0.12)

6.03 (0.14)

0.001

0.10

<.001

 6

Fusobacterium nucleatum_subsp._animalis

N

5.39 (0.07)

5.29 (0.14)

5.29 (0.10)

5.57 (0.12)

0.136

0.10

0.106

 7

Campylobacter gracilis

N

O

5.19 (0.05)

5.02 (0.11)

5.15 (0.07)

5.33 (0.09)

0.052

0.10

0.016

 8

Fusobacterium nucleatum_subsp._polymorphum

N

O

5.19 (0.07)

5.36 (0.15)

5.28 (0.09)

4.97 (0.12)

0.052

−0.10

0.019

 9

Prevotella oris

N

5.08 (0.09)

5.25 (0.18)

5.05 (0.13)

5.03 (0.16)

0.646

−0.10

0.118

 10

Streptococcus sanguinis

N

Y

4.91 (0.07)

5.57 (0.15)

5.04 (0.10)

4.38 (0.13)

<.001*

−0.18

<.001*

 11

Corynebacterium matruchotii

N

4.81 (0.07)

4.87 (0.17)

4.86 (0.10)

4.70 (0.12)

0.550

−0.04

0.171

 12

Selenomonas noxia

N

4.81 (0.08)

4.63 (0.18)

4.69 (0.11)

5.06 (0.13)

0.049

0.10

<.001

 13

Prevotella nigrescens

N

O

4.31 (0.10)

4.48 (0.21)

4.28 (0.15)

4.26 (0.18)

0.714

− 0.03

0.370

 14

Parvimonas micra

N

4.29 (0.08)

4.08 (0.17)

4.35 (0.11)

4.33 (0.12)

0.401

0.00

0.967

 15

Rothia dentocariosa

U

4.28 (0.09)

4.46 (0.19)

4.38 (0.13)

4.04 (0.15)

0.113

−0.10

0.008

 16

Fusobacterium sp._oral_taxon_203

N

4.23 (0.10)

4.08 (0.22)

4.36 (0.15)

4.16 (0.17)

0.497

−0.01

0.713

 17

Streptococcus gordonii

N

Y

4.19 (0.08)

3.93 (0.18)

4.15 (0.12)

4.40 (0.13)

0.090

0.04

0.039

 18

Granulicatella adiacens

N

4.15 (0.06)

4.23 (0.14)

4.11 (0.09)

4.15 (0.10)

0.749

0.00

0.991

 19

Streptococcus intermedius

N

Y

3.94 (0.10)

4.33 (0.21)

3.86 (0.15)

3.81 (0.16)

0.119

−0.10

0.016

 20

Actinomyces naeslundii

N

B

3.85 (0.06)

4.00 (0.14)

3.88 (0.09)

3.72 (0.11)

0.230

−0.10

0.008

20 Least Abundant Species

 1

Porphyrobacter tepidarius

N

− 3.58 (0.03)

−3.51 (0.08)

− 3.65 (0.05)

− 3.54 (0.06)

0.216

0.01

0.869

 2

Sphingomonas sp._oral_taxon_006

P

− 3.55 (0.04)

− 3.49 (0.08)

− 3.60 (0.05)

− 3.52 (0.06)

0.407

−0.00

0.989

 3

Pyramidobacter piscolens

P

− 3.53 (0.04)

− 3.44 (0.10)

− 3.60 (0.06)

− 3.47 (0.07)

0.251

− 0.01

0.919

 4

Leptothrix sp._oral_taxon_025

P

−3.50 (0.04)

− 3.37 (0.08)

− 3.53 (0.06)

−3.53 (0.06)

0.216

−0.04

0.221

 5

Treponema sp._oral_taxon_247

P

−3.45 (0.05)

−3.35 (0.09)

− 3.50 (0.07)

−3.44 (0.08)

0.436

− 0.02

0.566

 6

Atopobium sp._oral_taxon_416

P

−3.38 (0.05)

−3.45 (0.09)

− 3.44 (0.07)

−3.27 (0.09)

0.202

0.10

0.042

 7

Brevundimonas diminuta

N

−3.30 (0.04)

−3.17 (0.09)

− 3.35 (0.06)

−3.30 (0.07)

0.232

−0.03

0.306

 8

Prevotella multiformis

N

−3.08 (0.06)

−3.12 (0.11)

− 3.10 (0.09)

−3.05 (0.10)

0.901

0.03

0.359

 9

GN02_[G-2] sp._oral_taxon_873

P

−3.06 (0.05)

−3.08 (0.12)

− 3.03 (0.08)

−3.10 (0.09)

0.851

−0.00

0.927

 10

Streptococcus sobrinus

U

−3.04 (0.06)

−3.21 (0.10)

− 3.19 (0.09)

−2.75 (0.14)

0.005

0.11

<.001*

 11

Aggregatibacter actinomycetemcomitans

P

− 3.01 (0.07)

− 2.97 (0.15)

− 3.09 (0.10)

− 2.94 (0.11)

0.575

0.03

0.349

 12

Fretibacterium sp._oral_taxon_361

P

−2.98 (0.06)

−3.18 (0.10)

−2.97 (0.09)

− 2.88 (0.11)

0.207

0.02

0.469

 13

Butyrivibrio sp._oral_taxon_080

P

−2.96 (0.06)

−2.85 (0.13)

− 2.90 (0.09)

−3.10 (0.09)

0.193

−0.10

0.038

 14

Lactobacillus gasseri

N

−2.95 (0.06)

−3.08 (0.12)

−3.09 (0.09)

−2.70 (0.12)

0.012

0.10

0.002

 15

Mitsuokella sp._oral_taxon_521

N

−2.90 (0.06)

−2.91 (0.12)

− 2.92 (0.08)

−2.87 (0.11)

0.929

0.02

0.603

 16

Microbacterium flavescens

P

−2.89 (0.04)

−2.73 (0.09)

− 2.89 (0.06)

−2.97 (0.07)

0.151

−0.10

0.051

 17

Prevotella sp._oral_taxon_475

N

−2.87 (0.06)

−2.81 (0.12)

− 2.84 (0.09)

−2.95 (0.09)

0.575

−0.04

0.157

 18

Neisseria pharyngis

N

−2.87 (0.06)

−2.81 (0.13)

− 2.95 (0.09)

−2.80 (0.11)

0.479

0.01

0.760

 19

Fretibacterium sp._oral_taxon_358

U

−2.84 (0.07)

−2.87 (0.14)

− 2.88 (0.10)

−2.77 (0.12)

0.708

0.02

0.494

 20

Treponema medium

P

−2.79 (0.06)

−2.85 (0.14)

− 2.74 (0.10)

−2.81 (0.10)

0.777

0.02

0.579

*OTUs are ranked according to mean CLR OTU. The 20 most abundant OTUs have positive mean CRL; the 20 least abundant OTUs have negative mean CLR

The CLR OTU can be interpreted as a log [2] fold-difference for the given species relative to the overall compositional geometric mean. A mean CLR of 3 indicates a 8-fold [23] higher abundance, and a mean CLR of −3 indicates a 8-fold lower abundance, relative to the overall compositional geometric mean

SE standard error, Pearson r the Pearson product-moment correlation coefficient

p-values: bolded are significant at alpha .05; asterisk are significant at alpha 0.05 after Bonferroni correction

Culture status annotation in HOMD: N = named; U = unnamed; P = phylotyped

Socransky complex32: R = red; O = orange; P = purple; G = green; Y = yellow; B = blue; −-- = not part of the Socransky classification

Linear correlations (Table 3) among the 20 most abundant bacteria ranged from r = − 0.18 to r = 0.10, with 11 (55%) of the correlations achieving statistical significance (uncorrected P < 0.05; bolded). After Bonferroni correction, only 1 (9%) of these remained statistically significant (S. sanguinis, r = − 0.18; corrected P < 0.001). Among the 20 least abundant bacteria, linear correlations ranged from − 0.10 to 0.11. Four (20%) correlations achieved statistical significance (uncorrected P < 0.05; bolded), of which 1 (25%) remained significant after Bonferonni correction (Streptococcus sobrinus, r = 0.11; corrected P < 0.001).

Differences in mean CLR across age categories achieved statistical significance (P < 0.05) for 8 (40%) of the 20 most abundant bacteria, of which only 1 (12.5%) remained significant following Bonferroni correction (S. sanguinis, corrected P < 0.001). Mean CLR differences across age categories among the least abundant bacteria were significant (P < 0.05) for two bacteria, neither of which remained significant after Bonferroni correction.

Table 4 presents the rank ordered mean CLR OTUs for all 267 taxa identified, as well as their linear correlations with age, culture status and Socransky classification. A total of 148 (55.4%) taxa had names previously annotated in the HOMD database, whereas 60 (22.5%) were unnamed and are OTUs potentially identifying new bacteria. In the overall cohort, 117 (43.8%) taxa demonstrated elevated abundance (CLR > 0), the remaining 150 (57.3%) demonstrating reduced abundance (CLR < 0), relative to the overall composition mean. Twenty eight (10.5%) taxa that demonstrated a 8-fold (i.e., 23) or greater elevation in abundance based on mean CLR OTUs. There were 15 (5.6%) taxa with a 8-fold lower abundance relative to the overall composition mean. Of the virulent periodontal pathogens included in Socransky’s classification, [34] only T. forsythia (mean CLR, 1.87) and F. nucleatum (mean CLR, 6.4) had an elevated abundance, whereas T. denticola (mean CLR, − 0.28), P. gingivalis (mean CLR, − 0.56), P. intermedia (mean CLR, − 1.36) were, on average, in lower abundance. Several bacteria associated with healthy periodontium were in higher abundance: S. oralis (mean CLR, 5.5), sanguinis (mean CLR, 3.4), gordonii (mean CLR, 2.8), and intermedius (mean CLR, 2.6); P. micra (mean CLR, 3.0).
Table 4

Mean CLR OTUs for each of 267 bacterial species in the overall cohort and by age categories, and its linear correlation with age

Rank Order*

OTU Label

Culture Status

Socransky Complex

Overall

Cohort

(N = 1219)

Age Categories (years)

Linear Correlation

    

CLR OTU

Mean (SE)

50–59

(N = 239)

CLR OTU

Mean (SE)

60–69

(N = 554)

CLR OTU

Mean (SE)

≥70

(N = 426)

CLR OTU

Mean (SE)

p-value

Pearson r

p-value

1

Veillonella dispar

N

8.25 (0.06)

8.23 (0.13)

8.11 (0.09)

8.45 (0.10)

0.045

0.08

0.008

2

Streptococcus oralis

N

Y

8.06 (0.05)

8.40 (0.11)

8.06 (0.08)

7.87 (0.09)

0.002

−0.10

<.001

3

Veillonella parvula

N

P

7.60 (0.07)

7.48 (0.15)

7.45 (0.09)

7.86 (0.11)

0.014

0.10

0.001

4

Fusobacterium nucleatum_subsp._vincentii

N

O

6.43 (0.08)

6.21 (0.17)

6.48 (0.11)

6.50 (0.13)

0.356

0.02

0.587

5

Selenomonas sputigena

N

5.63 (0.08)

5.34 (0.17)

5.44 (0.12)

6.03 (0.14)

0.001

0.10

<.001

6

Fusobacterium nucleatum_subsp._animalis

N

5.39 (0.07)

5.29 (0.14)

5.29 (0.10)

5.57 (0.12)

0.136

0.10

0.106

7

Campylobacter gracilis

N

O

5.19 (0.05)

5.02 (0.11)

5.15 (0.07)

5.33 (0.09)

0.052

0.10

0.016

8

Fusobacterium nucleatum_subsp._polymorphum

N

O

5.19 (0.07)

5.36 (0.15)

5.28 (0.09)

4.97 (0.12)

0.052

−0.10

0.019

9

Prevotella oris

N

5.08 (0.09)

5.25 (0.18)

5.05 (0.13)

5.03 (0.16)

0.646

−0.10

0.118

10

Streptococcus sanguinis

N

Y

4.91 (0.07)

5.57 (0.15)

5.04 (0.10)

4.38 (0.13)

<.001*

−0.18

<.001*

11

Corynebacterium matruchotii

N

4.81 (0.07)

4.87 (0.17)

4.86 (0.10)

4.70 (0.12)

0.550

−0.04

0.171

12

Selenomonas noxia

N

4.81 (0.08)

4.63 (0.18)

4.69 (0.11)

5.06 (0.13)

0.049

0.10

<.001

13

Prevotella nigrescens

N

O

4.31 (0.10)

4.48 (0.21)

4.28 (0.15)

4.26 (0.18)

0.714

−0.03

0.370

14

Parvimonas micra

N

4.29 (0.08)

4.08 (0.17)

4.35 (0.11)

4.33 (0.12)

0.401

0.00

0.967

15

Rothia dentocariosa

U

4.28 (0.09)

4.46 (0.19)

4.38 (0.13)

4.04 (0.15)

0.113

−0.10

0.008

16

Fusobacterium sp._oral_taxon_203

N

4.23 (0.10)

4.08 (0.22)

4.36 (0.15)

4.16 (0.17)

0.497

−0.01

0.713

17

Streptococcus gordonii

N

Y

4.19 (0.08)

3.93 (0.18)

4.15 (0.12)

4.40 (0.13)

0.090

0.04

0.039

18

Granulicatella adiacens

N

4.15 (0.06)

4.23 (0.14)

4.11 (0.09)

4.15 (0.10)

0.749

0.00

0.991

19

Streptococcus intermedius

N

Y

3.94 (0.10)

4.33 (0.21)

3.86 (0.15)

3.81 (0.16)

0.119

−0.10

0.016

20

Actinomyces naeslundii

N

B

3.85 (0.06)

4.00 (0.14)

3.88 (0.09)

3.72 (0.11)

0.230

−0.10

0.008

21

TM7_[G-1] sp._oral_taxon_346

P

3.78 (0.09)

3.63 (0.19)

3.90 (0.12)

3.70 (0.16)

0.421

0.00

0.917

22

Haemophilus parainfluenzae

N

3.74 (0.09)

4.21 (0.19)

3.73 (0.13)

3.48 (0.15)

0.014

−0.10

0.004

23

Fusobacterium naviforme

N

3.58 (0.08)

3.61 (0.18)

3.62 (0.12)

3.52 (0.14)

0.852

−0.03

0.294

24

Dialister invisus

N

3.51 (0.08)

3.12 (0.16)

3.50 (0.11)

3.75 (0.13)

0.013

0.10

0.003

25

Capnocytophaga gingivalis

N

G

3.36 (0.08)

3.39 (0.18)

3.45 (0.11)

3.23 (0.13)

0.423

−0.04

0.172

26

Streptococcus cristatus

N

3.27 (0.07)

3.17 (0.16)

3.27 (0.11)

3.32 (0.13)

0.776

0.01

0.754

27

Gemella morbillorum

N

3.14 (0.09)

3.37 (0.20)

3.35 (0.13)

2.73 (0.16)

0.004

−0.11

<.001*

28

Streptococcus salivarius

U

3.02 (0.08)

3.05 (0.18)

2.79 (0.13)

3.29 (0.14)

0.028

0.10

0.090

29

TM7_[G-1] sp._oral_taxon_349

N

2.99 (0.10)

2.71 (0.22)

3.15 (0.14)

2.95 (0.18)

0.251

0.04

0.204

30

Bacteroidales_[G-2] sp._oral_taxon_274

N

2.96 (0.10)

2.47 (0.22)

3.15 (0.14)

3.00 (0.16)

0.030

0.03

0.328

31

Campylobacter showae

P

O

2.89 (0.08)

3.00 (0.17)

2.81 (0.11)

2.93 (0.14)

0.609

−0.01

0.685

32

Veillonella atypica

N

2.88 (0.09)

2.47 (0.20)

2.56 (0.13)

3.53 (0.14)

<.001*

0.16

<.001*

33

Eikenella corrodens

N

2.87 (0.07)

3.00 (0.15)

3.07 (0.10)

2.53 (0.12)

0.001

−0.11

<.001*

34

Capnocytophaga leadbetteri

N

2.86 (0.09)

2.87 (0.20)

2.93 (0.13)

2.78 (0.16)

0.758

−0.03

0.334

35

Fretibacterium sp._oral_taxon_360

N

2.81 (0.11)

2.29 (0.23)

2.89 (0.16)

3.00 (0.19)

0.048

0.04

0.148

36

Prevotella sp._oral_taxon_317

N

2.73 (0.10)

2.79 (0.22)

2.68 (0.16)

2.76 (0.18)

0.907

−0.00

0.965

37

Capnocytophaga granulosa

U

2.72 (0.09)

2.39 (0.21)

2.84 (0.13)

2.75 (0.16)

0.189

0.04

0.152

38

Alloprevotella tannerae

N

2.71 (0.12)

2.69 (0.24)

2.78 (0.17)

2.64 (0.20)

0.865

0.01

0.788

39

Kingella oralis

P

2.66 (0.08)

2.66 (0.19)

2.65 (0.11)

2.68 (0.14)

0.983

−0.01

0.847

40

TM7_[G-1] sp._oral_taxon_952

U

2.58 (0.10)

2.80 (0.22)

2.83 (0.14)

2.12 (0.16)

0.002

−0.10

<.001

41

Selenomonas artemidis

N

2.51 (0.11)

2.77 (0.24)

2.39 (0.16)

2.52 (0.19)

0.419

−0.00

0.957

42

Campylobacter concisus

N

G

2.41 (0.06)

2.22 (0.14)

2.37 (0.10)

2.56 (0.11)

0.152

0.10

0.036

43

Actinomyces oris

N

B

2.36 (0.08)

2.63 (0.17)

2.37 (0.11)

2.18 (0.13)

0.104

−0.10

0.021

44

Treponema socranskii

N

2.22 (0.07)

1.84 (0.17)

2.16 (0.11)

2.52 (0.13)

0.004

0.10

<.001

45

Cardiobacterium hominis

N

2.21 (0.08)

2.50 (0.19)

2.45 (0.12)

1.75 (0.14)

<.001*

−0.11

<.001

46

Leptotrichia wadei

N

2.15 (0.10)

2.21 (0.23)

1.94 (0.16)

2.38 (0.18)

0.159

0.03

0.305

47

Anaeroglobus geminatus

P

2.12 (0.10)

1.32 (0.22)

1.94 (0.15)

2.79 (0.18)

<.001*

0.17

<.001*

48

Gemella haemolysans

N

2.11 (0.09)

2.42 (0.20)

2.10 (0.13)

1.96 (0.14)

0.161

−0.10

0.018

49

Capnocytophaga sputigena

N

G

2.11 (0.09)

2.31 (0.21)

2.23 (0.13)

1.84 (0.17)

0.113

−0.10

0.094

50

Rothia aeria

N

2.11 (0.09)

2.49 (0.20)

2.42 (0.14)

1.48 (0.15)

<.001*

−0.15

<.001*

51

Bergeyella sp._oral_taxon_322

N

2.08 (0.07)

2.38 (0.16)

2.11 (0.10)

1.87 (0.11)

0.028

−0.10

0.008

52

Leptotrichia hongkongensis

N

2.02 (0.09)

2.02 (0.21)

1.94 (0.14)

2.13 (0.16)

0.660

0.03

0.337

53

Rothia mucilaginosa

U

1.95 (0.08)

1.79 (0.17)

1.90 (0.11)

2.09 (0.13)

0.321

0.03

0.237

54

Prevotella melaninogenica

N

1.90 (0.08)

1.75 (0.17)

1.78 (0.12)

2.14 (0.14)

0.095

0.10

0.049

55

Actinomyces sp._oral_taxon_169

N

1.89 (0.09)

2.28 (0.20)

1.96 (0.13)

1.59 (0.15)

0.016

−0.10

<.001

56

Tannerella forsythia

N

R

1.87 (0.10)

1.50 (0.21)

1.80 (0.14)

2.18 (0.17)

0.042

0.10

0.029

57

Selenomonas sp._oral_taxon_136

N

1.86 (0.08)

1.21 (0.18)

1.76 (0.12)

2.36 (0.15)

<.001*

0.16

<.001*

58

Catonella morbi

N

1.86 (0.08)

2.08 (0.17)

1.89 (0.11)

1.69 (0.13)

0.184

−0.10

0.020

59

Prevotella denticola

N

1.74 (0.10)

1.46 (0.23)

1.60 (0.15)

2.10 (0.18)

0.040

0.10

0.006

60

Neisseria sicca

N

1.72 (0.11)

1.58 (0.25)

1.88 (0.16)

1.60 (0.18)

0.416

−0.01

0.678

61

Peptostreptococcaceae_[XI][G-9] [Eubacterium]_brac

U

1.70 (0.08)

2.08 (0.16)

1.72 (0.12)

1.47 (0.14)

0.030

−0.10

0.003

62

Neisseria elongata

N

1.63 (0.10)

1.95 (0.25)

1.81 (0.15)

1.22 (0.17)

0.012

−0.10

0.008

63

Cardiobacterium valvarum

U

1.49 (0.09)

1.60 (0.21)

1.63 (0.13)

1.26 (0.14)

0.137

−0.10

0.044

64

Porphyromonas sp._oral_taxon_279

P

1.49 (0.09)

1.46 (0.20)

1.62 (0.13)

1.34 (0.16)

0.394

−0.02

0.494

65

Selenomonas infelix

U

1.48 (0.08)

1.56 (0.17)

1.44 (0.12)

1.50 (0.15)

0.871

−0.01

0.709

66

Leptotrichia sp._oral_taxon_212

U

1.44 (0.09)

1.63 (0.21)

1.64 (0.13)

1.08 (0.16)

0.013

−0.10

0.011

67

Actinomyces sp._oral_taxon_180

N

1.44 (0.07)

1.54 (0.15)

1.45 (0.10)

1.38 (0.11)

0.704

−0.03

0.235

68

Prevotella sp._oral_taxon_300

N

1.43 (0.09)

1.31 (0.19)

1.24 (0.13)

1.75 (0.15)

0.025

0.10

0.007

69

Prevotella maculosa

N

1.42 (0.08)

1.07 (0.17)

1.32 (0.11)

1.75 (0.13)

0.003

0.10

0.001

70

Streptococcus mutans

N

1.39 (0.11)

0.98 (0.24)

1.19 (0.16)

1.87 (0.20)

0.005

0.10

<.001

71

Actinomyces massiliensis

N

B

1.38 (0.07)

1.68 (0.17)

1.50 (0.10)

1.05 (0.11)

0.002

−0.12

<.001*

72

Fretibacterium fastidiosum

N

1.30 (0.10)

1.12 (0.22)

1.25 (0.15)

1.47 (0.17)

0.393

0.04

0.173

73

Veillonellaceae_[G-1] sp._oral_taxon_150

N

1.23 (0.09)

0.74 (0.20)

1.00 (0.13)

1.81 (0.16)

<.001*

0.14

<.001*

74

Neisseria flavescens

N

1.23 (0.10)

0.98 (0.21)

1.28 (0.14)

1.30 (0.17)

0.425

0.02

0.533

75

Prevotella oulorum

P

1.22 (0.09)

1.23 (0.20)

1.00 (0.13)

1.50 (0.15)

0.041

0.10

0.059

76

Streptococcus anginosus

N

Y

1.17 (0.11)

1.03 (0.23)

0.92 (0.16)

1.56 (0.19)

0.024

0.10

0.013

77

Lachnoanaerobaculum saburreum

N

1.07 (0.08)

0.85 (0.18)

1.12 (0.12)

1.13 (0.14)

0.384

0.04

0.208

78

Veillonellaceae_[G-1] sp._oral_taxon_155

N

1.00 (0.09)

0.66 (0.20)

0.84 (0.13)

1.39 (0.15)

0.004

0.10

<.001

79

Selenomonas sp._oral_taxon_892

L

0.98 (0.08)

1.18 (0.19)

1.05 (0.12)

0.76 (0.15)

0.148

−0.10

0.030

80

Actinomyces johnsonii

N

B

0.97 (0.07)

1.18 (0.16)

0.92 (0.11)

0.92 (0.12)

0.365

−0.04

0.229

81

Selenomonas sp._oral_taxon_137

U

0.95 (0.11)

0.95 (0.25)

1.21 (0.17)

0.61 (0.20)

0.064

−0.04

0.145

82

Corynebacterium durum

U

0.93 (0.08)

1.53 (0.19)

1.07 (0.12)

0.42 (0.13)

<.001*

−0.15

<.001*

83

Lautropia mirabilis

U

0.88 (0.09)

1.28 (0.21)

0.99 (0.13)

0.53 (0.15)

0.006

−0.10

<.001

84

Veillonella rogosae

N

0.87 (0.09)

1.06 (0.20)

1.08 (0.13)

0.49 (0.16)

0.010

−0.10

<.001

85

Leptotrichia sp._oral_taxon_417

N

0.86 (0.09)

0.41 (0.20)

0.95 (0.13)

1.01 (0.16)

0.048

0.10

0.006

86

Selenomonas flueggei

N

0.81 (0.08)

0.58 (0.18)

0.81 (0.12)

0.93 (0.14)

0.317

0.04

0.122

87

Selenomonas sp._oral_taxon_134

P

0.77 (0.10)

0.55 (0.21)

0.75 (0.14)

0.94 (0.18)

0.367

0.03

0.251

88

Streptococcus parasanguinis_II

U

0.74 (0.09)

0.58 (0.19)

0.49 (0.13)

1.15 (0.15)

0.003

0.11

<.001*

89

Megasphaera micronuciformis

N

0.70 (0.08)

0.47 (0.19)

0.46 (0.13)

1.14 (0.14)

<.001

0.12

<.001*

90

Capnocytophaga sp._oral_taxon_336

N

0.69 (0.09)

0.68 (0.19)

0.69 (0.13)

0.71 (0.16)

0.991

0.02

0.480

91

Oribacterium sp._oral_taxon_078

U

0.66 (0.08)

−0.03 (0.17)

0.51 (0.11)

1.26 (0.14)

<.001*

0.18

<.001*

92

Actinomyces sp._oral_taxon_171

P

0.66 (0.08)

0.82 (0.18)

0.66 (0.12)

0.57 (0.13)

0.527

−0.10

0.090

93

Lachnospiraceae_[G-3] sp._oral_taxon_100

U

0.59 (0.08)

0.60 (0.18)

0.73 (0.12)

0.41 (0.14)

0.200

−0.03

0.239

94

Parvimonas sp._oral_taxon_393

U

0.58 (0.11)

1.11 (0.24)

0.63 (0.16)

0.22 (0.17)

0.010

−0.12

<.001*

95

Actinomyces gerencseriae

N

B

0.56 (0.07)

0.49 (0.17)

0.37 (0.11)

0.86 (0.13)

0.012

0.10

0.008

96

Dialister pneumosintes

P

0.55 (0.09)

0.64 (0.20)

0.42 (0.14)

0.65 (0.16)

0.477

0.03

0.357

97

Kingella denitrificans

N

0.54 (0.09)

0.21 (0.20)

0.45 (0.13)

0.84 (0.15)

0.025

0.10

0.024

98

Porphyromonas endodontalis

N

0.52 (0.12)

1.09 (0.27)

0.56 (0.17)

0.13 (0.20)

0.015

−0.10

<.001

99

TM7_[G-5] sp._oral_taxon_356

P

0.49 (0.11)

0.30 (0.23)

0.61 (0.16)

0.43 (0.19)

0.517

0.02

0.580

100

Selenomonas sp._oral_taxon_919

U

0.47 (0.08)

0.72 (0.18)

0.45 (0.12)

0.35 (0.15)

0.287

−0.10

0.096

101

Leptotrichia buccalis

N

0.45 (0.10)

0.23 (0.23)

0.77 (0.14)

0.16 (0.16)

0.011

−0.03

0.375

102

Prevotella sp._oral_taxon_472

N

0.45 (0.10)

0.65 (0.23)

0.80 (0.15)

−0.13 (0.17)

<.001*

−0.10

<.001

103

Capnocytophaga sp._oral_taxon_326

P

0.41 (0.10)

0.38 (0.23)

0.62 (0.15)

0.15 (0.17)

0.121

−0.10

0.080

104

Streptococcus constellatus

N

O

0.35 (0.10)

0.25 (0.21)

0.18 (0.15)

0.63 (0.17)

0.114

0.04

0.139

105

Prevotella salivae

N

0.34 (0.08)

−0.22 (0.18)

0.32 (0.12)

0.69 (0.14)

<.001

0.15

<.001*

106

Leptotrichia sp._oral_taxon_392

U

0.33 (0.09)

0.49 (0.20)

0.58 (0.13)

− 0.08 (0.15)

0.003

−0.10

0.001

107

Actinobaculum sp._oral_taxon_183

N

0.32 (0.08)

0.29 (0.17)

0.28 (0.12)

0.40 (0.14)

0.765

0.01

0.742

108

Neisseria oralis

U

0.31 (0.11)

0.47 (0.25)

0.35 (0.15)

0.19 (0.18)

0.618

−0.04

0.133

109

Atopobium rimae

N

0.21 (0.09)

−0.08 (0.19)

0.17 (0.13)

0.43 (0.16)

0.124

0.10

0.108

110

Leptotrichia hofstadii

N

0.20 (0.10)

0.10 (0.22)

0.27 (0.15)

0.17 (0.17)

0.804

0.01

0.743

111

Streptococcus sp._oral_taxon_074

N

0.15 (0.07)

0.15 (0.16)

0.25 (0.11)

0.02 (0.12)

0.340

−0.04

0.154

112

Fretibacterium sp._oral_taxon_359

L

0.15 (0.11)

0.14 (0.25)

0.04 (0.16)

0.30 (0.18)

0.537

0.02

0.552

113

Leptotrichia shahii

U

0.11 (0.10)

0.30 (0.22)

−0.09 (0.15)

0.26 (0.19)

0.209

0.03

0.298

114

Tannerella sp._oral_taxon_286

U

0.11 (0.07)

− 0.15 (0.16)

0.26 (0.10)

0.06 (0.13)

0.101

0.03

0.370

115

Porphyromonas sp._oral_taxon_284

N

0.08 (0.10)

0.14 (0.21)

0.22 (0.14)

− 0.14 (0.16)

0.223

−0.10

0.080

116

Peptostreptococcaceae_[XI][G-7] [Eubacterium]_yuri

P

0.05 (0.10)

0.50 (0.21)

0.19 (0.14)

−0.40 (0.16)

0.001

−0.14

<.001*

117

Selenomonas sp._oral_taxon_146

L

0.04 (0.08)

0.04 (0.18)

− 0.03 (0.12)

0.14 (0.14)

0.659

0.014

0.633

118

Fusobacterium periodonticum

N

O

−0.02 (0.07)

−0.12 (0.16)

0.13 (0.11)

−0.17 (0.13)

0.174

−0.02

0.488

119

Actinomyces meyeri

L

B

−0.04 (0.08)

0.29 (0.18)

0.05 (0.12)

− 0.35 (0.13)

0.010

−0.11

<.001*

120

Leptotrichia sp._oral_taxon_215

N

− 0.05 (0.08)

0.16 (0.18)

0.01 (0.12)

− 0.24 (0.14)

0.157

−0.04

0.170

121

Prevotella oralis

N

− 0.06 (0.10)

−0.34 (0.20)

− 0.13 (0.14)

0.20 (0.17)

0.105

0.10

0.030

122

Prevotella pleuritidis

N

− 0.10 (0.12)

−0.07 (0.27)

0.09 (0.18)

−0.38 (0.20)

0.211

−0.04

0.190

123

Abiotrophia defectiva

N

−0.15 (0.09)

−0.05 (0.19)

− 0.01 (0.13)

− 0.38 (0.14)

0.138

− 0.10

0.028

124

Gemella sanguinis

N

−0.19 (0.07)

−0.16 (0.15)

− 0.35 (0.10)

− 0.00 (0.12)

0.077

0.04

0.204

125

Fusobacterium nucleatum_subsp._nucleatum

N

O

−0.25 (0.08)

−0.44 (0.17)

− 0.30 (0.11)

− 0.08 (0.14)

0.209

0.03

0.259

126

Atopobium parvulum

N

− 0.25 (0.08)

−0.28 (0.17)

− 0.47 (0.11)

0.06 (0.14)

0.009

0.10

0.005

127

Aggregatibacter sp._oral_taxon_458

N

− 0.25 (0.09)

− 0.11 (0.19)

− 0.17 (0.13)

− 0.44 (0.15)

0.309

−0.10

0.047

128

Streptococcus parasanguinis_I

N

− 0.26 (0.08)

−0.29 (0.17)

− 0.48 (0.11)

0.05 (0.13)

0.008

0.10

0.008

129

Aggregatibacter aphrophilus

N

− 0.27 (0.11)

−0.18 (0.25)

− 0.01 (0.17)

− 0.66 (0.18)

0.027

− 0.10

0.015

130

Treponema denticola

N

R

−0.28 (0.10)

−0.16 (0.22)

− 0.25 (0.15)

− 0.39 (0.18)

0.692

− 0.04

0.211

131

Prevotella saccharolytica

U

− 0.37 (0.07)

− 0.38 (0.16)

− 0.26 (0.11)

− 0.51 (0.13)

0.336

− 0.01

0.663

132

TM7_[G-1] sp._oral_taxon_488

P

− 0.39 (0.10)

− 0.39 (0.22)

− 0.11 (0.15)

− 0.76 (0.16)

0.015

−0.04

0.132

133

Johnsonella ignava

U

− 0.41 (0.09)

−0.50 (0.21)

− 0.34 (0.14)

− 0.45 (0.16)

0.783

− 0.01

0.783

134

Actinomyces israelii

N

B

−0.47 (0.06)

−0.65 (0.13)

− 0.52 (0.09)

− 0.30 (0.11)

0.091

0.10

0.012

135

Lachnoanaerobaculum umeaense

P

− 0.47 (0.07)

−0.35 (0.17)

− 0.39 (0.11)

− 0.65 (0.12)

0.198

−0.03

0.316

136

Streptococcus sp._oral_taxon_056

U

− 0.49 (0.08)

−0.38 (0.19)

− 0.37 (0.12)

− 0.73 (0.14)

0.127

−0.04

0.050

137

Olsenella sp._oral_taxon_807

N

− 0.49 (0.07)

−0.93 (0.15)

− 0.50 (0.10)

− 0.25 (0.12)

0.002

0.11

<.001*

138

Solobacterium moorei

U

− 0.51 (0.06)

−0.49 (0.15)

− 0.60 (0.09)

− 0.42 (0.11)

0.437

0.04

0.221

139

Treponema maltophilum

P

− 0.53 (0.08)

−0.78 (0.16)

− 0.59 (0.11)

− 0.32 (0.13)

0.070

0.10

0.040

140

TM7_[G-1] sp._oral_taxon_348

N

− 0.53 (0.08)

− 0.66 (0.17)

− 0.29 (0.13)

− 0.77 (0.14)

0.026

− 0.03

0.373

141

Porphyromonas gingivalis

N

R

−0.56 (0.12)

−0.70 (0.26)

− 0.60 (0.17)

− 0.43 (0.22)

0.688

0.03

0.348

142

Centipeda periodontii

N

− 0.60 (0.08)

− 0.94 (0.15)

− 0.55 (0.11)

− 0.47 (0.13)

0.074

0.06

0.031

143

Selenomonas sp._oral_taxon_126

N

− 0.60 (0.08)

−0.77 (0.18)

− 0.56 (0.12)

− 0.56 (0.14)

0.588

0.03

0.386

144

Desulfobulbus sp._oral_taxon_041

U

−0.66 (0.10)

−1.02 (0.20)

− 0.70 (0.14)

− 0.40 (0.17)

0.064

0.10

0.027

145

Alloprevotella rava

U

−0.68 (0.08)

−0.78 (0.18)

− 0.64 (0.12)

− 0.69 (0.14)

0.809

0.02

0.464

146

Actinobaculum sp._oral_taxon_848

P

− 0.70 (0.08)

−0.83 (0.17)

− 0.82 (0.11)

−0.46 (0.13)

0.080

0.10

0.016

147

Stomatobaculum longum

N

− 0.70 (0.07)

− 0.95 (0.16)

− 0.76 (0.11)

−0.48 (0.13)

0.054

0.11

<.001

148

Prevotella histicola

N

− 0.75 (0.09)

− 0.96 (0.18)

−1.04 (0.13)

− 0.26 (0.16)

<.001

0.11

<.001*

149

Aggregatibacter segnis

U

− 0.79 (0.10)

− 0.42 (0.22)

− 0.69 (0.14)

−1.13 (0.15)

0.020

− 0.11

<.001*

150

Leptotrichia sp._oral_taxon_225

N

− 0.80 (0.10)

− 0.43 (0.22)

− 0.60 (0.15)

− 1.25 (0.15)

0.002

− 0.11

<.001*

151

Ruminococcaceae_[G-1] sp._oral_taxon_075

N

− 0.80 (0.08)

− 0.79 (0.17)

− 0.69 (0.12)

−0.94 (0.13)

0.350

−0.03

0.341

152

Peptostreptococcus stomatis

U

− 0.80 (0.09)

−0.50 (0.19)

− 0.77 (0.13)

− 1.02 (0.14)

0.085

− 0.10

0.032

153

Porphyromonas catoniae

P

− 0.92 (0.09)

− 0.50 (0.20)

− 0.79 (0.13)

−1.31 (0.14)

0.002

− 0.10

<.001

154

Actinomyces sp._oral_taxon_178

P

−0.93 (0.06)

− 1.15 (0.14)

− 0.94 (0.09)

− 0.78 (0.10)

0.099

0.05

0.080

155

Prevotella pallens

N

− 0.93 (0.08)

−1.00 (0.17)

− 1.05 (0.11)

−0.73 (0.14)

0.191

0.10

0.054

156

Filifactor alocis

U

− 0.94 (0.10)

−0.66 (0.23)

− 0.98 (0.15)

− 1.05 (0.18)

0.382

− 0.10

0.077

157

Selenomonas sp._oral_taxon_936

P

−0.96 (0.08)

− 0.91 (0.17)

−1.05 (0.12)

− 0.87 (0.14)

0.578

0.03

0.323

158

TM7_[G-1] sp._oral_taxon_347

N

− 0.97 (0.09)

−0.64 (0.20)

− 0.95 (0.14)

−1.17 (0.14)

0.107

− 0.10

0.071

159

Haemophilus sp._oral_taxon_036

N

−1.01 (0.09)

− 0.65 (0.19)

− 1.00 (0.13)

− 1.21 (0.15)

0.075

− 0.10

0.002

160

Prevotella sp._oral_taxon_292

P

− 1.06 (0.08)

− 1.34 (0.17)

− 1.15 (0.12)

−0.79 (0.15)

0.040

0.10

0.001

161

Leptotrichia sp._oral_taxon_498

N

− 1.07 (0.09)

−1.28 (0.20)

− 1.20 (0.13)

−0.77 (0.16)

0.059

0.10

0.013

162

Capnocytophaga sp._oral_taxon_338

U

− 1.08 (0.09)

−1.17 (0.20)

− 1.12 (0.13)

−0.98 (0.15)

0.671

0.01

0.808

163

Alloprevotella sp._oral_taxon_308

N

− 1.14 (0.07)

−0.90 (0.14)

−1.28 (0.10)

− 1.10 (0.12)

0.111

−0.01

0.799

164

Treponema sp._oral_taxon_231

P

− 1.15 (0.09)

−1.04 (0.18)

− 1.03 (0.13)

− 1.36 (0.15)

0.206

− 0.10

0.074

165

TM7_[G-1] sp._oral_taxon_352

N

− 1.15 (0.07)

− 1.31 (0.15)

− 1.11 (0.10)

− 1.11 (0.12)

0.545

0.04

0.173

166

Prevotella buccae

U

− 1.23 (0.07)

−1.71 (0.14)

− 1.36 (0.11)

− 0.78 (0.12)

<.001*

0.14

<.001*

167

Prevotella loescheii

N

−1.24 (0.09)

−0.96 (0.21)

−0.97 (0.14)

− 1.74 (0.15)

<.001

− 0.10

0.001

168

Capnocytophaga sp._oral_taxon_864

U

− 1.27 (0.08)

−0.98 (0.20)

−1.15 (0.13)

− 1.57 (0.13)

0.020

− 0.10

0.005

169

Actinomyces sp._oral_taxon_170

U

−1.29 (0.08)

− 0.99 (0.19)

− 1.16 (0.13)

− 1.62 (0.13)

0.011

− 0.10

<.001

170

Lachnoanaerobaculum orale

U

− 1.31 (0.07)

− 1.09 (0.16)

− 1.46 (0.09)

−1.23 (0.12)

0.085

0.02

0.513

171

Ottowia sp._oral_taxon_894

N

− 1.31 (0.08)

−1.44 (0.18)

− 1.24 (0.12)

− 1.33 (0.14)

0.662

−0.00

0.938

172

Streptococcus lactarius

N

− 1.32 (0.07)

− 1.06 (0.15)

− 1.46 (0.10)

− 1.30 (0.12)

0.097

−0.02

0.414

173

Peptostreptococcaceae_[XI][G-1] [Eubacterium]_infi

P

− 1.33 (0.07)

− 1.59 (0.15)

− 1.41 (0.09)

− 1.08 (0.12)

0.014

0.10

0.002

174

Leptotrichia sp._oral_taxon_219

N

− 1.34 (0.07)

−1.39 (0.17)

− 1.27 (0.11)

−1.39 (0.12)

0.736

−0.01

0.717

175

Prevotella intermedia

P

O

−1.36 (0.11)

−1.31 (0.25)

− 1.35 (0.17)

− 1.41 (0.18)

0.943

−0.04

0.181

176

Veillonella denticariosi

U

− 1.37 (0.09)

− 1.51 (0.19)

− 1.39 (0.13)

− 1.27 (0.15)

0.621

0.04

0.156

177

Fretibacterium sp._oral_taxon_362

N

− 1.43 (0.08)

−1.48 (0.19)

− 1.43 (0.12)

− 1.42 (0.14)

0.965

0.00

0.888

178

Bacteroidetes_[G-5] sp._oral_taxon_511

U

− 1.47 (0.09)

− 1.44 (0.19)

− 1.43 (0.14)

− 1.54 (0.15)

0.846

−0.03

0.378

179

Prevotella sp._oral_taxon_313

P

− 1.49 (0.08)

−1.14 (0.18)

− 1.75 (0.11)

− 1.35 (0.14)

0.007

0.02

0.431

180

TM7_[G-3] sp._oral_taxon_351

P

− 1.50 (0.06)

−1.84 (0.13)

− 1.39 (0.10)

− 1.45 (0.11)

0.029

0.10

0.018

181

Streptococcus australis

N

− 1.51 (0.07)

−1.62 (0.15)

− 1.57 (0.11)

− 1.38 (0.13)

0.373

0.03

0.295

182

Granulicatella elegans

N

− 1.59 (0.07)

−1.18 (0.17)

− 1.72 (0.11)

−1.65 (0.12)

0.023

−0.10

0.067

183

TM7_[G-1] sp._oral_taxon_869

P

− 1.60 (0.09)

−1.64 (0.20)

− 1.55 (0.14)

− 1.64 (0.15)

0.890

0.01

0.663

184

Capnocytophaga sp._oral_taxon_902

N

−1.65 (0.08)

− 1.56 (0.19)

− 1.68 (0.12)

−1.67 (0.14)

0.860

−0.04

0.220

185

Prevotella dentalis

P

−1.66 (0.08)

−1.65 (0.19)

− 1.82 (0.12)

−1.47 (0.14)

0.180

0.03

0.326

186

Campylobacter curvus

N

− 1.67 (0.07)

−1.57 (0.17)

− 1.79 (0.10)

− 1.58 (0.13)

0.365

0.03

0.335

187

Pseudoramibacter alactolyticus

P

− 1.68 (0.08)

− 2.18 (0.17)

−1.73 (0.12)

− 1.35 (0.15)

0.001

0.12

<.001*

188

TM7_[G-6] sp._oral_taxon_870

N

− 1.71 (0.08)

−1.47 (0.18)

− 1.69 (0.12)

− 1.85 (0.13)

0.220

−0.10

0.085

189

Veillonellaceae_[G-1] sp._oral_taxon_129

N

− 1.71 (0.08)

− 1.96 (0.16)

− 1.80 (0.11)

− 1.46 (0.14)

0.042

0.10

0.010

190

Tannerella sp._oral_taxon_808

U

− 1.75 (0.07)

−2.03 (0.14)

−1.70 (0.10)

− 1.65 (0.12)

0.104

0.10

0.011

191

Peptostreptococcaceae_[XI][G-6] [Eubacterium]_noda

L

− 1.75 (0.08)

− 1.67 (0.18)

− 1.90 (0.11)

−1.61 (0.14)

0.238

0.02

0.425

192

Mitsuokella sp._oral_taxon_131

N

− 1.79 (0.09)

−2.18 (0.17)

− 1.96 (0.13)

− 1.36 (0.16)

<.001

0.14

<.001*

193

Mycoplasma salivarium

P

− 1.80 (0.07)

−1.77 (0.15)

− 1.87 (0.11)

− 1.71 (0.12)

0.579

0.03

0.302

194

Haemophilus haemolyticus

P

− 1.81 (0.08)

−1.30 (0.19)

− 1.92 (0.12)

− 1.94 (0.12)

0.006

−0.10

0.043

195

Bergeyella sp._oral_taxon_907

P

−1.81 (0.07)

−1.86 (0.15)

− 1.72 (0.10)

− 1.92 (0.12)

0.405

− 0.01

0.765

196

TM7_[G-2] sp._oral_taxon_350

N

− 1.82 (0.09)

− 1.86 (0.18)

− 1.82 (0.13)

− 1.80 (0.15)

0.968

0.02

0.412

197

Prevotella veroralis

U

− 1.82 (0.08)

−1.73 (0.18)

− 1.78 (0.13)

− 1.93 (0.13)

0.582

−0.02

0.413

198

Aggregatibacter paraphrophilus

N

− 1.82 (0.09)

−1.48 (0.21)

− 1.69 (0.14)

−2.19 (0.13)

0.007

−0.10

<.001

199

Leptotrichia sp._oral_taxon_223

P

− 1.82 (0.08)

−1.71 (0.17)

− 1.98 (0.11)

− 1.69 (0.14)

0.206

0.02

0.499

200

Bifidobacterium dentium

N

− 1.85 (0.08)

−2.10 (0.18)

−2.12 (0.12)

−1.37 (0.15)

<.001*

0.15

<.001*

201

Alloprevotella sp._oral_taxon_473

U

− 1.87 (0.08)

−1.63 (0.17)

− 1.88 (0.12)

− 1.98 (0.13)

0.300

−0.10

0.030

202

Veillonellaceae_[G-1] sp._oral_taxon_145

U

− 1.88 (0.08)

−1.98 (0.16)

− 1.83 (0.12)

− 1.88 (0.14)

0.768

0.02

0.551

203

Neisseria bacilliformis

N

−1.89 (0.09)

−1.82 (0.20)

− 1.90 (0.13)

− 1.93 (0.14)

0.906

−0.04

0.194

204

Capnocytophaga sp._oral_taxon_412

N

− 1.89 (0.08)

−1.74 (0.18)

− 1.81 (0.12)

−2.09 (0.13)

0.173

− 0.04

0.162

205

Neisseria subflava

N

− 1.89 (0.09)

− 1.84 (0.18)

−2.04 (0.13)

− 1.73 (0.16)

0.267

0.10

0.118

206

Veillonella sp._oral_taxon_780

N

− 1.94 (0.08)

− 1.46 (0.20)

− 1.93 (0.12)

− 2.20 (0.12)

0.004

−0.10

<.001

207

Lachnospiraceae_[G-8] sp._oral_taxon_500

N

− 1.94 (0.07)

−1.91 (0.16)

−2.03 (0.10)

− 1.83 (0.12)

0.443

0.01

0.695

208

Capnocytophaga sp._oral_taxon_323

P

−1.94 (0.08)

−1.99 (0.17)

− 1.93 (0.12)

− 1.94 (0.14)

0.966

− 0.01

0.731

209

Scardovia wiggsiae

P

−1.94 (0.09)

− 2.07 (0.19)

− 2.11 (0.12)

− 1.66 (0.16)

0.061

0.10

0.009

210

Sphingomonas echinoides

N

− 1.95 (0.06)

−1.75 (0.14)

− 1.89 (0.10)

− 2.15 (0.11)

0.056

−0.10

<.001

211

SR1_[G-1] sp._oral_taxon_874

U

− 1.99 (0.07)

−1.76 (0.15)

− 1.88 (0.10)

−2.26 (0.11)

0.008

−0.10

0.006

212

Treponema lecithinolyticum

U

−2.01 (0.08)

−1.98 (0.17)

− 1.90 (0.12)

− 2.18 (0.13)

0.302

−0.10

0.068

213

Prevotella baroniae

P

−2.04 (0.07)

−2.20 (0.15)

− 2.03 (0.11)

− 1.96 (0.13)

0.490

0.04

0.209

214

Pseudomonas fluorescens

P

− 2.05 (0.07)

− 2.12 (0.15)

− 2.07 (0.11)

−1.98 (0.13)

0.767

0.03

0.334

215

Shuttleworthia satelles

P

− 2.08 (0.07)

− 2.27 (0.14)

− 2.21 (0.10)

−1.82 (0.12)

0.016

0.10

<.001

216

Prevotella sp._oral_taxon_306

U

 

−2.08 (0.07)

−2.32 (0.14)

− 2.21 (0.10)

−1.79 (0.13)

0.010

0.10

<.001

217

Porphyromonas sp._oral_taxon_275

N

− 2.11 (0.07)

−2.09 (0.16)

− 2.01 (0.12)

− 2.26 (0.12)

0.321

−0.04

0.184

218

Streptococcus sinensis

P

− 2.14 (0.06)

− 1.95 (0.13)

− 2.30 (0.08)

− 2.05 (0.11)

0.050

0.02

0.517

219

Anaerolineae_[G-1] sp._oral_taxon_439

N

− 2.14 (0.08)

− 2.47 (0.15)

− 2.22 (0.11)

−1.85 (0.14)

0.008

0.12

<.001*

220

Bacteroidaceae_[G-1] sp._oral_taxon_272

N

− 2.15 (0.07)

− 2.48 (0.15)

− 2.21 (0.10)

−1.87 (0.13)

0.007

0.10

<.001

221

Prevotella micans

N

− 2.15 (0.07)

−2.24 (0.14)

− 2.18 (0.10)

− 2.08 (0.12)

0.658

0.02

0.452

222

Leptotrichia goodfellowii

U

− 2.17 (0.07)

−1.90 (0.17)

−2.14 (0.11)

− 2.36 (0.12)

0.080

−0.10

0.008

223

Capnocytophaga sp._oral_taxon_903

N

− 2.17 (0.08)

−2.15 (0.17)

− 2.12 (0.11)

− 2.25 (0.13)

0.751

− 0.01

0.731

224

Peptostreptococcaceae_[XI][G-5] [Eubacterium]_saph

U

− 2.18 (0.08)

−2.46 (0.15)

− 2.13 (0.12)

− 2.08 (0.13)

0.195

0.04

0.229

225

Treponema sp._oral_taxon_237

P

− 2.20 (0.08)

−1.68 (0.19)

−2.21 (0.12)

− 2.46 (0.13)

0.003

−0.11

<.001*

226

Fusobacterium sp._oral_taxon_370

U

− 2.20 (0.06)

−2.25 (0.12)

− 2.08 (0.09)

− 2.32 (0.10)

0.176

−0.04

0.176

227

Atopobium sp._oral_taxon_199

U

− 2.26 (0.07)

−2.19 (0.16)

− 2.18 (0.11)

− 2.40 (0.12)

0.334

−0.02

0.433

228

Prevotella sp._oral_taxon_314

N

− 2.28 (0.07)

− 2.29 (0.16)

− 2.35 (0.11)

− 2.18 (0.13)

0.605

0.02

0.519

229

Capnocytophaga sp._oral_taxon_324

U

− 2.28 (0.07)

−2.43 (0.15)

− 2.24 (0.11)

− 2.25 (0.12)

0.588

0.03

0.256

230

Haemophilus parahaemolyticus

N

− 2.29 (0.08)

−1.86 (0.18)

−2.23 (0.12)

− 2.61 (0.11)

0.002

−0.11

<.001*

231

Porphyromonas sp._oral_taxon_278

U

− 2.29 (0.07)

−2.40 (0.14)

− 2.24 (0.11)

− 2.30 (0.12)

0.716

0.00

0.977

232

Selenomonas sp._oral_taxon_937

U

− 2.35 (0.06)

−2.34 (0.12)

− 2.46 (0.09)

− 2.22 (0.11)

0.203

0.03

0.386

233

Selenomonas dianae

N

− 2.36 (0.07)

− 2.52 (0.14)

− 2.27 (0.10)

− 2.38 (0.11)

0.367

0.02

0.569

234

Selenomonas sp._oral_taxon_133

U

− 2.37 (0.08)

− 2.25 (0.18)

− 2.40 (0.11)

− 2.41 (0.13)

0.719

−0.02

0.396

235

Selenomonas sp._oral_taxon_478

P

− 2.49 (0.06)

−2.54 (0.13)

− 2.46 (0.09)

− 2.49 (0.10)

0.882

0.03

0.306

236

Capnocytophaga sp._oral_taxon_332

U

− 2.50 (0.07)

−2.26 (0.16)

− 2.42 (0.11)

− 2.72 (0.11)

0.043

−0.10

0.043

237

Megasphaera sp._oral_taxon_123

N

− 2.51 (0.08)

− 2.06 (0.19)

− 2.51 (0.12)

− 2.77 (0.13)

0.009

− 0.10

0.002

238

Bradyrhizobium elkanii

U

− 2.54 (0.08)

−2.37 (0.17)

− 2.68 (0.11)

− 2.44 (0.13)

0.209

−0.00

0.900

239

Prevotella sp._oral_taxon_376

P

− 2.54 (0.07)

−2.22 (0.17)

− 2.49 (0.11)

− 2.79 (0.12)

0.015

−0.10

<.001

240

Prevotella sp._oral_taxon_526

P

− 2.56 (0.07)

−2.59 (0.14)

− 2.57 (0.10)

− 2.52 (0.12)

0.923

0.01

0.736

241

Selenomonas sp._oral_taxon_442

U

− 2.58 (0.05)

− 2.78 (0.11)

− 2.52 (0.09)

− 2.53 (0.09)

0.177

0.10

0.065

242

Leptotrichia sp._oral_taxon_879

U

− 2.60 (0.07)

− 2.56 (0.16)

− 2.62 (0.10)

−2.59 (0.11)

0.951

− 0.02

0.597

243

Selenomonas sp._oral_taxon_149

P

− 2.61 (0.06)

− 2.75 (0.12)

− 2.70 (0.09)

− 2.42 (0.10)

0.048

0.10

0.004

244

Aggregatibacter sp._oral_taxon_513

U

− 2.66 (0.07)

− 2.64 (0.14)

− 2.52 (0.11)

− 2.85 (0.11)

0.107

− 0.03

0.368

245

Treponema vincentii

N

− 2.67 (0.06)

−2.55 (0.13)

− 2.60 (0.09)

− 2.83 (0.09)

0.140

−0.04

0.125

246

Capnocytophaga sp._oral_taxon_380

N

− 2.70 (0.07)

−2.65 (0.14)

− 2.59 (0.11)

− 2.88 (0.11)

0.132

−0.10

0.107

247

Johnsonella sp._oral_taxon_166

U

− 2.78 (0.06)

−2.96 (0.12)

− 2.69 (0.10)

− 2.80 (0.11)

0.292

−0.01

0.855

248

Treponema medium

P

−2.79 (0.06)

− 2.85 (0.14)

− 2.74 (0.10)

−2.81 (0.10)

0.777

0.02

0.579

249

Fretibacterium sp._oral_taxon_358

U

− 2.84 (0.07)

−2.87 (0.14)

− 2.88 (0.10)

− 2.77 (0.12)

0.708

0.02

0.494

250

Neisseria pharyngis

N

− 2.87 (0.06)

−2.81 (0.13)

− 2.95 (0.09)

− 2.80 (0.11)

0.479

0.01

0.760

251

Prevotella sp._oral_taxon_475

N

− 2.87 (0.06)

−2.81 (0.12)

− 2.84 (0.09)

− 2.95 (0.09)

0.575

−0.04

0.157

252

Microbacterium flavescens

P

− 2.89 (0.04)

− 2.73 (0.09)

− 2.89 (0.06)

−2.97 (0.07)

0.151

−0.10

0.051

253

Mitsuokella sp._oral_taxon_521

N

− 2.90 (0.06)

−2.91 (0.12)

− 2.92 (0.08)

− 2.87 (0.11)

0.929

0.02

0.603

254

Lactobacillus gasseri

N

− 2.95 (0.06)

−3.08 (0.12)

− 3.09 (0.09)

−2.70 (0.12)

0.012

0.10

0.002

255

Butyrivibrio sp._oral_taxon_080

P

− 2.96 (0.06)

−2.85 (0.13)

− 2.90 (0.09)

−3.10 (0.09)

0.193

−0.10

0.038

256

Fretibacterium sp._oral_taxon_361

P

− 2.98 (0.06)

− 3.18 (0.10)

− 2.97 (0.09)

− 2.88 (0.11)

0.207

0.02

0.469

257

Aggregatibacter actinomycetemcomitans

P

− 3.01 (0.07)

−2.97 (0.15)

−3.09 (0.10)

−2.94 (0.11)

0.575

0.03

0.349

258

Streptococcus sobrinus

U

− 3.04 (0.06)

−3.21 (0.10)

− 3.19 (0.09)

−2.75 (0.14)

0.005

0.11

<.001*

259

GN02_[G-2] sp._oral_taxon_873

P

− 3.06 (0.05)

−3.08 (0.12)

− 3.03 (0.08)

− 3.10 (0.09)

0.851

−0.00

0.927

260

Prevotella multiformis

N

− 3.08 (0.06)

− 3.12 (0.11)

− 3.10 (0.09)

− 3.05 (0.10)

0.901

0.03

0.359

261

Brevundimonas diminuta

N

− 3.30 (0.04)

− 3.17 (0.09)

− 3.35 (0.06)

− 3.30 (0.07)

0.232

−0.03

0.306

262

Atopobium sp._oral_taxon_416

P

− 3.38 (0.05)

− 3.45 (0.09)

− 3.44 (0.07)

− 3.27 (0.09)

0.202

0.10

0.042

263

Treponema sp._oral_taxon_247

P

− 3.45 (0.05)

− 3.35 (0.09)

− 3.50 (0.07)

− 3.44 (0.08)

0.436

− 0.02

0.566

264

Leptothrix sp._oral_taxon_025

P

− 3.50 (0.04)

−3.37 (0.08)

− 3.53 (0.06)

− 3.53 (0.06)

0.216

− 0.04

0.221

265

Pyramidobacter piscolens

P

− 3.53 (0.04)

− 3.44 (0.10)

− 3.60 (0.06)

−3.47 (0.07)

0.251

− 0.01

0.919

266

Sphingomonas sp._oral_taxon_006

P

− 3.55 (0.04)

−3.49 (0.08)

− 3.60 (0.05)

− 3.52 (0.06)

0.407

− 0.00

0.989

267

Porphyrobacter tepidarius

N

−3.58 (0.03)

−3.51 (0.08)

− 3.65 (0.05)

−3.54 (0.06)

0.216

0.01

0.869

Rank order, OTUs are sorted high to low, with most abundant OTU at the top of the table

The CLR OTU is interpreted as a log [2] fold-difference for the given species relative to the overall compositional geometric mean. A mean CLR of 3 indicates a 8-fold [23] higher abundance, and a mean CLR of − 3 indicates a 8-fold lower abundance, relative to the overall compositional geometric mean

SE standard error, Pearson r the Pearson product-moment correlation coefficient

p-values: bolded are significant at alpha 0.05; asterisk are significant at alpha 0.05 after Bonferroni correction

Culture status: N = named; U = unnamed; P = phylotyped

Socransky complex32: R = red; O = orange; P = purple; G = green; Y = yellow; B = blue; −-- = not part of the Socransky classification

Among all 1219 women (Table 4), Pearson correlations ranged from r = − 0.18 to r = 0.18. Eighty two (31%) taxa were significantly correlated with age (uncorrected P < 0.05; bolded), of which 28 (34.2%) remained significant after Bonferroni correction. The largest positive correlation was with Oribacterium sp._oral_taxon 078 (r = 0.18; corrected P < 0.001); the most negative correlation was with Strep. sanguinis (r = − 0.18; corrected P < .001). Correlations between established pathogenic bacteria from Socransky’s complex [34] and age were of weak (T. denticola, r = − 0.04; P. gingivalis, r = 0.03; F. nucleatum, r = 0.03) to moderate (Fusobacterium nucleatum polymorphum, r = − 0.10; T. forsythia, r = 0.10) magnitude. Bacteria associated with healthy periodontium were correlated with age on a similar (S. oralis, r = − 0.10; intermedius r = − 0.10; mutans, r = 0.10) or somewhat stronger (S. sanguinis, r = − 0.16) magnitude.

Ninety (33.7%) bacteria were observed to be significantly different across age categories (uncorrected P < 0.05; bolded in Table 4), of which 12 (13.3%) remained significant after Bonferroni correction (corrected P < 0.05). Fig. 5 presents box-and-whisker plots depicting the variability of CLR OTUs for the 12 bacteria that were significantly different across age groups (corrected P < 0.001). Of these 12 bacteria, 7 were significantly higher in older than younger women; whilst the remaining 5 were higher in the younger women. Bifidobacterium dentium showed the greatest difference (0.73 CLR OTU units) between age groups among the bacteria observed to be higher in older women, whereas S. sanguinis showed the largest difference (1.19 CLR OTU units) between age groups for bacteria higher in younger women.
Fig. 5

Box plots of mean CLR OTUs that differed between age categories (corrected P < 0.05). Box reflects the 25th, 50th, and 75th percentile CLR OTU; whiskers reflect the range of CLR OTU

Tables 5 and 6 present additional measures used in previous studies to characterize the oral microbiome. Relative abundance for the overall cohort and according to age categories is shown in Table 5, ranked high to low, with dashed lines denoting the top 20 taxa. V. dispar demonstrated the highest relative abundance (mean, 8.9%), and the remaining bacterial order is quite similar to the top 20 when ordered according to CLR mean OTU (Table 2). Patterns of relative abundance across age categories also were generally comparable to those observed for CLR mean OTUs. Bacterial prevalence (present at any abundance) is shown in Table 6, for which a slightly different ordering is noted for the top 20 most prevalent bacteria compared to those ordered on CLR OTU or relative abundance. There were 12 (4.5%) bacteria prevalent at 99% or higher and 3 (1.1%) present in all samples (S. oralis, V. dispar and parvula). Differences in prevalence across age categories were modest. Among all women, prevalence of established pathogenic bacteria in Socransky’s complex was 86.8, 82.9 56.6, and 55.1% for F. nucleatum, T. forsythia, T. denticola, and P. gingivalis, respectively. Prevalence of T. forsythia did not vary consistently with age, whereas prevalence of F. nucleatum and T. denticola tended to decline with age and P. gingivalis tended to increase with age.
Table 5

Mean Relative Abundance for each of 267 bacterial species, overall and by age categories

Rank Ordera

OTU label

Overall

(N = 1219)

50–59

(N = 239)

60–69

(N = 554)

≥70

(N = 426)

Relative Abundance (%)

Mean (SE)

Relative Abundance (%)

Mean (SE)

Relative Abundance (%)

Mean (SE)

Relative Abundance (%)

Mean (SE)

1

Veillonella dispar

8.94 (0.26)

8.66 (0.52)

8.52 (0.37)

9.64 (0.48)

2

Streptococcus oralis

7.68 (0.24)

9.52 (0.60)

7.95 (0.39)

6.29 (0.31)

3

Veillonella parvula

6.57 (0.22)

6.14 (0.44)

6.07 (0.30)

7.46 (0.42)

4

Fusobacterium nucleatum_subsp._vincentii

4.00 (0.14)

3.82 (0.32)

4.11 (0.21)

3.97 (0.23)

5

Selenomonas sputigena

2.94 (0.12)

2.23 (0.20)

2.66 (0.16)

3.70 (0.25)

6

Fusobacterium sp._oral_taxon_203

2.35 (0.13)

2.15 (0.28)

2.63 (0.21)

2.09 (0.20)

7

Prevotella oris

1.85 (0.07)

1.81 (0.14)

1.89 (0.11)

1.81 (0.10)

8

Prevotella nigrescens

1.78 (0.07)

1.64 (0.13)

1.81 (0.11)

1.81 (0.12)

9

Fusobacterium nucleatum_subsp._animalis

1.65 (0.06)

1.54 (0.13)

1.63 (0.09)

1.74 (0.09)

10

Selenomonas noxia

1.48 (0.07)

1.52 (0.18)

1.45 (0.11)

1.50 (0.11)

11

Fusobacterium nucleatum_subsp._polymorphum

1.42 (0.04)

1.57 (0.11)

1.50 (0.07)

1.24 (0.07)

12

Rothia dentocariosa

1.41 (0.10)

1.43 (0.17)

1.60 (0.18)

1.16 (0.13)

13

Streptococcus sanguinis

1.40 (0.07)

1.83 (0.14)

1.40 (0.09)

1.16 (0.13)

14

Alloprevotella tannerae

1.39 (0.07)

1.22 (0.16)

1.46 (0.12)

1.41 (0.11)

15

Haemophilus parainfluenzae

1.21 (0.09)

1.62 (0.24)

1.15 (0.13)

1.07 (0.14)

16

Corynebacterium matruchotii

1.17 (0.05)

1.34 (0.13)

1.24 (0.07)

0.99 (0.06)

17

Fretibacterium sp._oral_taxon_360

1.15 (0.07)

0.89 (0.13)

1.24 (0.11)

1.19 (0.10)

18

Streptococcus intermedius

1.05 (0.05)

1.27 (0.12)

1.13 (0.08)

0.84 (0.05)

19

TM7_[G-1] sp._oral_taxon_349

1.04 (0.06)

0.97 (0.14)

0.97 (0.07)

1.18 (0.14)

20

Streptococcus gordonii

1.03 (0.05)

0.98 (0.15)

1.01 (0.07)

1.09 (0.10)

21

TM7_[G-1] sp._oral_taxon_346

1.02 (0.05)

1.01 (0.11)

1.05 (0.07)

1.00 (0.08)

22

Porphyromonas gingivalis

0.94 (0.10)

0.95 (0.27)

0.74 (0.10)

1.21 (0.19)

23

Campylobacter gracilis

0.94 (0.02)

0.90 (0.06)

0.96 (0.04)

0.95 (0.04)

24

Fusobacterium naviforme

0.89 (0.06)

0.91 (0.13)

0.92 (0.10)

0.83 (0.07)

25

Parvimonas micra

0.88 (0.03)

0.87 (0.07)

0.96 (0.05)

0.78 (0.05)

26

Neisseria sicca

0.80 (0.07)

0.83 (0.21)

0.87 (0.11)

0.69 (0.09)

27

Leptotrichia wadei

0.79 (0.06)

0.81 (0.15)

0.74 (0.08)

0.86 (0.11)

28

Selenomonas artemidis

0.79 (0.05)

0.87 (0.12)

0.75 (0.07)

0.79 (0.08)

29

Bacteroidales_[G-2] sp._oral_taxon_274

0.79 (0.04)

0.64 (0.08)

0.85 (0.07)

0.79 (0.06)

30

Prevotella sp._oral_taxon_317

0.77 (0.04)

0.67 (0.07)

0.80 (0.05)

0.78 (0.06)

31

Anaeroglobus geminatus

0.67 (0.04)

0.43 (0.08)

0.58 (0.06)

0.92 (0.09)

32

Capnocytophaga granulosa

0.65 (0.03)

0.63 (0.09)

0.66 (0.05)

0.64 (0.06)

33

Streptococcus salivarius

0.64 (0.05)

0.61 (0.09)

0.67 (0.09)

0.64 (0.07)

34

TM7_[G-1] sp._oral_taxon_952

0.64 (0.03)

0.72 (0.08)

0.71 (0.05)

0.50 (0.05)

35

Prevotella denticola

0.62 (0.05)

0.49 (0.07)

0.57 (0.08)

0.76 (0.09)

36

Capnocytophaga leadbetteri

0.61 (0.03)

0.59 (0.07)

0.63 (0.05)

0.61 (0.07)

37

Gemella morbillorum

0.61 (0.02)

0.69 (0.07)

0.65 (0.04)

0.52 (0.04)

38

Veillonella atypica

0.61 (0.05)

0.50 (0.09)

0.55 (0.07)

0.75 (0.08)

39

Streptococcus mutans

0.60 (0.05)

0.47 (0.09)

0.51 (0.07)

0.80 (0.10)

40

Fretibacterium sp._oral_taxon_359

0.60 (0.06)

0.77 (0.17)

0.60 (0.09)

0.49 (0.07)

41

Prevotella intermedia

0.59 (0.06)

0.62 (0.15)

0.63 (0.09)

0.52 (0.09)

42

Dialister invisus

0.57 (0.02)

0.47 (0.04)

0.60 (0.04)

0.60 (0.04)

43

Granulicatella adiacens

0.56 (0.02)

0.65 (0.05)

0.55 (0.03)

0.53 (0.03)

44

Porphyromonas endodontalis

0.55 (0.04)

0.63 (0.08)

0.57 (0.05)

0.49 (0.06)

45

Streptococcus cristatus

0.55 (0.03)

0.51 (0.07)

0.59 (0.05)

0.53 (0.04)

46

Capnocytophaga gingivalis

0.55 (0.03)

0.60 (0.07)

0.55 (0.04)

0.51 (0.04)

47

Prevotella pleuritidis

0.53 (0.04)

0.51 (0.08)

0.56 (0.06)

0.51 (0.06)

48

Neisseria elongata

0.53 (0.04)

0.66 (0.10)

0.55 (0.05)

0.43 (0.07)

49

Actinomyces naeslundii

0.52 (0.02)

0.62 (0.05)

0.53 (0.03)

0.46 (0.03)

50

Selenomonas sp._oral_taxon_137

0.51 (0.04)

0.51 (0.09)

0.52 (0.05)

0.50 (0.07)

51

Tannerella forsythia

0.49 (0.03)

0.42 (0.06)

0.46 (0.04)

0.58 (0.05)

52

TM7_[G-5] sp._oral_taxon_356

0.47 (0.03)

0.36 (0.07)

0.51 (0.06)

0.48 (0.06)

53

Campylobacter showae

0.46 (0.02)

0.44 (0.04)

0.47 (0.04)

0.46 (0.03)

54

Fretibacterium fastidiosum

0.46 (0.03)

0.54 (0.10)

0.45 (0.04)

0.42 (0.04)

55

Rothia aeria

0.45 (0.03)

0.45 (0.05)

0.55 (0.06)

0.33 (0.04)

56

Capnocytophaga sputigena

0.45 (0.03)

0.47 (0.05)

0.44 (0.04)

0.46 (0.05)

57

Gemella haemolysans

0.44 (0.04)

0.54 (0.08)

0.45 (0.07)

0.38 (0.06)

58

Leptotrichia hongkongensis

0.43 (0.03)

0.36 (0.04)

0.44 (0.05)

0.44 (0.05)

59

Neisseria flavescens

0.42 (0.04)

0.29 (0.06)

0.38 (0.06)

0.55 (0.09)

60

Neisseria oralis

0.42 (0.05)

0.59 (0.15)

0.32 (0.04)

0.45 (0.11)

61

Streptococcus anginosus

0.42 (0.03)

0.38 (0.05)

0.38 (0.04)

0.49 (0.06)

62

Aggregatibacter aphrophilus

0.37 (0.04)

0.33 (0.05)

0.45 (0.07)

0.28 (0.05)

63

Kingella oralis

0.36 (0.02)

0.41 (0.05)

0.31 (0.02)

0.39 (0.04)

64

Leptotrichia shahii

0.36 (0.04)

0.32 (0.07)

0.26 (0.03)

0.50 (0.08)

65

Leptotrichia buccalis

0.35 (0.03)

0.36 (0.07)

0.40 (0.05)

0.29 (0.05)

66

Selenomonas sp._oral_taxon_134

0.34 (0.02)

0.23 (0.04)

0.32 (0.03)

0.43 (0.05)

67

Leptotrichia hofstadii

0.33 (0.04)

0.42 (0.11)

0.34 (0.05)

0.27 (0.05)

68

Leptotrichia sp._oral_taxon_417

0.32 (0.03)

0.23 (0.04)

0.36 (0.05)

0.32 (0.05)

69

Cardiobacterium hominis

0.32 (0.02)

0.47 (0.08)

0.33 (0.02)

0.23 (0.02)

70

Selenomonas sp._oral_taxon_136

0.31 (0.02)

0.20 (0.03)

0.29 (0.03)

0.40 (0.04)

71

Eikenella corrodens

0.31 (0.01)

0.34 (0.03)

0.33 (0.02)

0.25 (0.02)

72

Prevotella melaninogenica

0.30 (0.02)

0.25 (0.03)

0.28 (0.03)

0.36 (0.04)

73

Porphyromonas sp._oral_taxon_279

0.30 (0.02)

0.28 (0.04)

0.32 (0.04)

0.30 (0.03)

74

Treponema denticola

0.28 (0.02)

0.26 (0.05)

0.28 (0.03)

0.31 (0.04)

75

Filifactor alocis

0.28 (0.02)

0.29 (0.05)

0.29 (0.04)

0.27 (0.04)

76

Actinomyces oris

0.28 (0.02)

0.31 (0.04)

0.27 (0.02)

0.27 (0.03)

77

Parvimonas sp._oral_taxon_393

0.28 (0.02)

0.36 (0.05)

0.28 (0.02)

0.23 (0.02)

78

Veillonellaceae_[G-1] sp._oral_taxon_150

0.27 (0.02)

0.22 (0.04)

0.23 (0.02)

0.35 (0.03)

79

Actinomyces sp._oral_taxon_169

0.27 (0.02)

0.39 (0.06)

0.26 (0.02)

0.22 (0.03)

80

Leptotrichia sp._oral_taxon_212

0.27 (0.02)

0.28 (0.03)

0.28 (0.02)

0.24 (0.04)

81

Rothia mucilaginosa

0.27 (0.02)

0.21 (0.03)

0.28 (0.04)

0.29 (0.03)

82

Selenomonas infelix

0.27 (0.02)

0.21 (0.02)

0.27 (0.03)

0.29 (0.03)

83

Cardiobacterium valvarum

0.25 (0.01)

0.31 (0.04)

0.26 (0.02)

0.21 (0.02)

84

Capnocytophaga sp._oral_taxon_326

0.25 (0.02)

0.26 (0.04)

0.28 (0.03)

0.22 (0.03)

85

Prevotella sp._oral_taxon_472

0.25 (0.02)

0.30 (0.05)

0.27 (0.02)

0.19 (0.02)

86

Treponema socranskii

0.25 (0.01)

0.22 (0.02)

0.24 (0.01)

0.27 (0.02)

87

Streptococcus constellatus

0.25 (0.02)

0.19 (0.03)

0.25 (0.03)

0.28 (0.03)

88

Veillonella rogosae

0.24 (0.02)

0.21 (0.04)

0.27 (0.04)

0.23 (0.03)

89

Fusobacterium nucleatum_subsp._nucleatum

0.24 (0.03)

0.21 (0.06)

0.19 (0.04)

0.34 (0.07)

90

Prevotella sp._oral_taxon_300

0.23 (0.01)

0.24 (0.03)

0.20 (0.01)

0.27 (0.03)

91

Veillonellaceae_[G-1] sp._oral_taxon_155

0.23 (0.02)

0.20 (0.03)

0.20 (0.02)

0.28 (0.03)

92

Campylobacter concisus

0.22 (0.01)

0.20 (0.02)

0.23 (0.01)

0.23 (0.02)

93

Leptotrichia sp._oral_taxon_225

0.22 (0.02)

0.26 (0.06)

0.28 (0.04)

0.12 (0.03)

94

Selenomonas sp._oral_taxon_892

0.22 (0.01)

0.24 (0.04)

0.21 (0.02)

0.21 (0.02)

95

Catonella morbi

0.21 (0.01)

0.23 (0.02)

0.21 (0.01)

0.19 (0.01)

96

Aggregatibacter segnis

0.20 (0.02)

0.21 (0.05)

0.24 (0.04)

0.15 (0.02)

97

Prevotella oulorum

0.20 (0.01)

0.21 (0.03)

0.18 (0.01)

0.22 (0.02)

98

Leptotrichia sp._oral_taxon_392

0.19 (0.01)

0.20 (0.04)

0.22 (0.02)

0.16 (0.02)

99

Dialister pneumosintes

0.19 (0.01)

0.18 (0.03)

0.19 (0.02)

0.20 (0.02)

100

Veillonella denticariosi

0.19 (0.03)

0.17 (0.06)

0.17 (0.04)

0.22 (0.07)

101

Peptostreptococcaceae_[XI][G-9] [Eubacterium]_brac

0.19 (0.01)

0.21 (0.02)

0.19 (0.01)

0.17 (0.01)

102

Megasphaera micronuciformis

0.19 (0.02)

0.15 (0.03)

0.17 (0.02)

0.23 (0.04)

103

Lautropia mirabilis

0.18 (0.01)

0.23 (0.03)

0.20 (0.02)

0.14 (0.01)

104

Streptococcus parasanguinis_II

0.18 (0.02)

0.15 (0.03)

0.17 (0.02)

0.21 (0.03)

105

Porphyromonas sp._oral_taxon_284

0.18 (0.01)

0.18 (0.02)

0.19 (0.02)

0.17 (0.02)

106

Selenomonas sp._oral_taxon_919

0.18 (0.01)

0.18 (0.02)

0.17 (0.02)

0.20 (0.03)

107

Bergeyella sp._oral_taxon_322

0.18 (0.01)

0.22 (0.02)

0.19 (0.01)

0.14 (0.01)

108

Leptotrichia sp._oral_taxon_498

0.18 (0.02)

0.14 (0.03)

0.16 (0.03)

0.22 (0.04)

109

Kingella denitrificans

0.17 (0.01)

0.17 (0.04)

0.17 (0.02)

0.18 (0.02)

110

Prevotella maculosa

0.17 (0.01)

0.16 (0.02)

0.16 (0.01)

0.18 (0.01)

111

Atopobium rimae

0.17 (0.01)

0.12 (0.02)

0.15 (0.02)

0.21 (0.03)

112

Corynebacterium durum

0.17 (0.01)

0.24 (0.03)

0.16 (0.01)

0.13 (0.03)

113

TM7_[G-1] sp._oral_taxon_488

0.17 (0.02)

0.23 (0.07)

0.18 (0.02)

0.11 (0.01)

114

Capnocytophaga sp._oral_taxon_336

0.17 (0.01)

0.15 (0.02)

0.17 (0.01)

0.17 (0.02)

115

Selenomonas flueggei

0.16 (0.01)

0.15 (0.03)

0.16 (0.02)

0.18 (0.03)

116

Aggregatibacter sp._oral_taxon_458

0.16 (0.02)

0.14 (0.02)

0.16 (0.02)

0.17 (0.03)

117

Fretibacterium sp._oral_taxon_362

0.16 (0.02)

0.15 (0.04)

0.18 (0.04)

0.14 (0.03)

118

Neisseria subflava

0.16 (0.02)

0.14 (0.04)

0.16 (0.04)

0.17 (0.03)

119

Peptostreptococcaceae_[XI][G-7] [Eubacterium]_yuri

0.16 (0.01)

0.18 (0.02)

0.17 (0.01)

0.12 (0.01)

120

TM7_[G-1] sp._oral_taxon_869

0.16 (0.03)

0.15 (0.04)

0.20 (0.06)

0.11 (0.02)

121

Lachnoanaerobaculum saburreum

0.15 (0.01)

0.14 (0.02)

0.15 (0.01)

0.15 (0.01)

122

Prevotella oralis

0.15 (0.01)

0.09 (0.01)

0.13 (0.01)

0.20 (0.02)

123

TM7_[G-2] sp._oral_taxon_350

0.15 (0.02)

0.12 (0.03)

0.14 (0.02)

0.17 (0.04)

124

Megasphaera sp._oral_taxon_123

0.14 (0.03)

0.17 (0.05)

0.12 (0.03)

0.15 (0.06)

125

Aggregatibacter paraphrophilus

0.14 (0.02)

0.18 (0.06)

0.18 (0.03)

0.07 (0.02)

126

Desulfobulbus sp._oral_taxon_041

0.14 (0.01)

0.11 (0.02)

0.13 (0.02)

0.17 (0.02)

127

Actinomyces massiliensis

0.14 (0.01)

0.18 (0.02)

0.15 (0.02)

0.10 (0.01)

128

Johnsonella ignava

0.13 (0.01)

0.13 (0.02)

0.14 (0.01)

0.13 (0.01)

129

Prevotella loescheii

0.13 (0.01)

0.15 (0.03)

0.15 (0.02)

0.09 (0.02)

130

Lachnospiraceae_[G-3] sp._oral_taxon_100

0.13 (0.01)

0.12 (0.01)

0.14 (0.01)

0.12 (0.01)

131

Actinomyces johnsonii

0.13 (0.01)

0.12 (0.01)

0.13 (0.02)

0.12 (0.02)

132

TM7_[G-1] sp._oral_taxon_347

0.12 (0.02)

0.16 (0.05)

0.14 (0.02)

0.08 (0.02)

133

Bacteroidetes_[G-5] sp._oral_taxon_511

0.12 (0.01)

0.10 (0.02)

0.13 (0.02)

0.12 (0.02)

134

Actinomyces sp._oral_taxon_180

0.12 (0.01)

0.13 (0.01)

0.12 (0.01)

0.10 (0.01)

135

Prevotella salivae

0.12 (0.01)

0.09 (0.02)

0.12 (0.01)

0.13 (0.02)

136

Actinomyces sp._oral_taxon_171

0.12 (0.01)

0.12 (0.02)

0.12 (0.01)

0.11 (0.01)

137

Selenomonas sp._oral_taxon_146

0.12 (0.01)

0.12 (0.02)

0.11 (0.01)

0.12 (0.01)

138

Abiotrophia defectiva

0.12 (0.01)

0.14 (0.03)

0.13 (0.01)

0.09 (0.01)

139

Pseudomonas fluorescens

0.11 (0.05)

0.07 (0.04)

0.15 (0.10)

0.10 (0.04)

140

Veillonella sp._oral_taxon_780

0.11 (0.02)

0.16 (0.06)

0.12 (0.04)

0.08 (0.03)

141

Porphyromonas catoniae

0.11 (0.01)

0.13 (0.03)

0.13 (0.02)

0.08 (0.01)

142

Mitsuokella sp._oral_taxon_131

0.11 (0.02)

0.05 (0.01)

0.11 (0.03)

0.14 (0.04)

143

Actinobaculum sp._oral_taxon_183

0.11 (0.01)

0.12 (0.02)

0.11 (0.01)

0.09 (0.01)

144

Oribacterium sp._oral_taxon_078

0.11 (0.01)

0.07 (0.01)

0.10 (0.01)

0.14 (0.01)

145

Treponema sp._oral_taxon_237

0.11 (0.01)

0.11 (0.03)

0.10 (0.02)

0.11 (0.02)

146

Haemophilus sp._oral_taxon_036

0.10 (0.01)

0.11 (0.03)

0.10 (0.02)

0.09 (0.02)

147

Leptotrichia sp._oral_taxon_215

0.10 (0.01)

0.12 (0.02)

0.10 (0.01)

0.08 (0.01)

148

Prevotella histicola

0.10 (0.01)

0.06 (0.01)

0.08 (0.02)

0.15 (0.03)

149

TM7_[G-1] sp._oral_taxon_348

0.10 (0.01)

0.08 (0.01)

0.12 (0.01)

0.09 (0.01)

150

Peptostreptococcus stomatis

0.10 (0.01)

0.11 (0.02)

0.10 (0.01)

0.08 (0.01)

151

Prevotella veroralis

0.10 (0.01)

0.08 (0.02)

0.12 (0.02)

0.08 (0.02)

152

Streptococcus sp._oral_taxon_056

0.10 (0.01)

0.11 (0.02)

0.09 (0.01)

0.09 (0.01)

153

Selenomonas sp._oral_taxon_126

0.10 (0.01)

0.09 (0.02)

0.10 (0.01)

0.09 (0.01)

154

Treponema sp._oral_taxon_231

0.09 (0.01)

0.07 (0.01)

0.10 (0.01)

0.09 (0.01)

155

Neisseria bacilliformis

0.09 (0.01)

0.11 (0.04)

0.08 (0.01)

0.08 (0.02)

156

Actinomyces gerencseriae

0.09 (0.01)

0.09 (0.01)

0.08 (0.01)

0.09 (0.01)

157

Prevotella dentalis

0.08 (0.01)

0.08 (0.02)

0.08 (0.02)

0.08 (0.01)

158

Fusobacterium periodonticum

0.08 (0.01)

0.06 (0.01)

0.09 (0.01)

0.09 (0.01)

159

Prevotella pallens

0.08 (0.01)

0.08 (0.02)

0.06 (0.01)

0.11 (0.02)

160

Centipeda periodontii

0.08 (0.01)

0.05 (0.01)

0.10 (0.01)

0.08 (0.01)

161

Scardovia wiggsiae

0.08 (0.01)

0.09 (0.03)

0.07 (0.02)

0.09 (0.02)

162

Streptococcus sp._oral_taxon_074

0.08 (0.01)

0.07 (0.01)

0.09 (0.01)

0.07 (0.01)

163

Haemophilus parahaemolyticus

0.08 (0.02)

0.09 (0.03)

0.11 (0.03)

0.04 (0.02)

164

Tannerella sp._oral_taxon_286

0.08 (0.00)

0.06 (0.01)

0.08 (0.01)

0.08 (0.01)

165

Selenomonas sp._oral_taxon_936

0.08 (0.01)

0.06 (0.01)

0.07 (0.01)

0.10 (0.02)

166

Actinomyces sp._oral_taxon_170

0.08 (0.01)

0.06 (0.01)

0.10 (0.02)

0.06 (0.02)

167

Ruminococcaceae_[G-1] sp._oral_taxon_075

0.08 (0.01)

0.09 (0.02)

0.08 (0.01)

0.07 (0.01)

168

Bifidobacterium dentium

0.08 (0.01)

0.07 (0.02)

0.06 (0.01)

0.10 (0.02)

169

Alloprevotella rava

0.08 (0.01)

0.07 (0.01)

0.07 (0.01)

0.09 (0.01)

170

Atopobium parvulum

0.08 (0.01)

0.06 (0.01)

0.06 (0.01)

0.11 (0.02)

171

Ottowia sp._oral_taxon_894

0.08 (0.01)

0.08 (0.02)

0.09 (0.01)

0.06 (0.01)

172

Prevotella sp._oral_taxon_313

0.07 (0.01)

0.09 (0.02)

0.05 (0.01)

0.10 (0.03)

173

TM7_[G-6] sp._oral_taxon_870

0.07 (0.01)

0.08 (0.02)

0.08 (0.01)

0.06 (0.01)

174

Capnocytophaga sp._oral_taxon_864

0.07 (0.01)

0.08 (0.01)

0.08 (0.01)

0.05 (0.01)

175

Actinomyces meyeri

0.07 (0.00)

0.08 (0.01)

0.08 (0.01)

0.06 (0.00)

176

Leptotrichia sp._oral_taxon_223

0.07 (0.01)

0.05 (0.01)

0.07 (0.02)

0.09 (0.02)

177

Capnocytophaga sp._oral_taxon_338

0.07 (0.00)

0.07 (0.01)

0.07 (0.01)

0.07 (0.01)

178

Streptococcus parasanguinis_I

0.07 (0.01)

0.06 (0.01)

0.06 (0.01)

0.08 (0.01)

179

Pseudoramibacter alactolyticus

0.07 (0.01)

0.10 (0.05)

0.05 (0.01)

0.07 (0.01)

180

Haemophilus haemolyticus

0.07 (0.01)

0.15 (0.05)

0.05 (0.01)

0.05 (0.01)

181

Neisseria pharyngis

0.07 (0.02)

0.06 (0.03)

0.04 (0.02)

0.10 (0.05)

182

Treponema maltophilum

0.07 (0.00)

0.06 (0.01)

0.06 (0.00)

0.08 (0.01)

183

Bradyrhizobium elkanii

0.07 (0.02)

0.12 (0.06)

0.05 (0.01)

0.05 (0.02)

184

Alloprevotella sp._oral_taxon_473

0.07 (0.01)

0.05 (0.01)

0.08 (0.02)

0.06 (0.01)

185

Streptococcus lactarius

0.06 (0.01)

0.11 (0.04)

0.05 (0.01)

0.06 (0.01)

186

Prevotella sp._oral_taxon_292

0.06 (0.00)

0.05 (0.01)

0.06 (0.01)

0.08 (0.01)

187

Capnocytophaga sp._oral_taxon_332

0.06 (0.01)

0.08 (0.04)

0.07 (0.01)

0.05 (0.01)

188

Prevotella saccharolytica

0.06 (0.00)

0.06 (0.01)

0.07 (0.01)

0.06 (0.00)

189

Leptotrichia sp._oral_taxon_879

0.06 (0.02)

0.14 (0.11)

0.03 (0.01)

0.05 (0.01)

190

Prevotella sp._oral_taxon_314

0.06 (0.01)

0.05 (0.02)

0.05 (0.01)

0.07 (0.01)

191

Actinobaculum sp._oral_taxon_848

0.06 (0.00)

0.04 (0.01)

0.06 (0.01)

0.06 (0.01)

192

Fretibacterium sp._oral_taxon_358

0.06 (0.01)

0.04 (0.02)

0.06 (0.02)

0.06 (0.01)

193

Streptococcus sobrinus

0.06 (0.01)

0.00 (0.00)

0.03 (0.01)

0.12 (0.04)

194

Aggregatibacter actinomycetemcomitans

0.06 (0.01)

0.06 (0.02)

0.06 (0.02)

0.05 (0.02)

195

Treponema lecithinolyticum

0.06 (0.01)

0.06 (0.01)

0.05 (0.01)

0.06 (0.01)

196

Capnocytophaga sp._oral_taxon_902

0.06 (0.01)

0.08 (0.02)

0.05 (0.01)

0.05 (0.01)

197

Peptostreptococcaceae_[XI][G-5] [Eubacterium]_saph

0.06 (0.01)

0.04 (0.01)

0.07 (0.01)

0.05 (0.01)

198

Lachnoanaerobaculum umeaense

0.06 (0.00)

0.06 (0.01)

0.06 (0.01)

0.05 (0.01)

199

Peptostreptococcaceae_[XI][G-6] [Eubacterium]_noda

0.05 (0.00)

0.06 (0.01)

0.05 (0.01)

0.06 (0.01)

200

Veillonellaceae_[G-1] sp._oral_taxon_145

0.05 (0.01)

0.04 (0.01)

0.05 (0.01)

0.06 (0.01)

201

TM7_[G-1] sp._oral_taxon_352

0.05 (0.01)

0.05 (0.01)

0.05 (0.01)

0.06 (0.01)

202

Capnocytophaga sp._oral_taxon_412

0.05 (0.01)

0.05 (0.01)

0.05 (0.01)

0.06 (0.01)

203

Gemella sanguinis

0.05 (0.00)

0.04 (0.01)

0.05 (0.01)

0.06 (0.01)

204

Aggregatibacter sp._oral_taxon_513

0.05 (0.01)

0.03 (0.02)

0.07 (0.01)

0.04 (0.01)

205

Selenomonas sp._oral_taxon_133

0.05 (0.01)

0.06 (0.02)

0.05 (0.01)

0.05 (0.01)

206

Granulicatella elegans

0.05 (0.01)

0.06 (0.01)

0.05 (0.01)

0.05 (0.01)

207

Veillonellaceae_[G-1] sp._oral_taxon_129

0.05 (0.01)

0.03 (0.01)

0.04 (0.01)

0.07 (0.02)

208

Selenomonas dianae

0.05 (0.01)

0.04 (0.02)

0.04 (0.01)

0.07 (0.03)

209

Prevotella sp._oral_taxon_526

0.05 (0.01)

0.02 (0.01)

0.06 (0.02)

0.05 (0.01)

210

Porphyromonas sp._oral_taxon_275

0.05 (0.01)

0.04 (0.01)

0.06 (0.01)

0.03 (0.01)

211

Anaerolineae_[G-1] sp._oral_taxon_439

0.05 (0.01)

0.04 (0.01)

0.04 (0.01)

0.06 (0.01)

212

Stomatobaculum longum

0.05 (0.00)

0.04 (0.01)

0.04 (0.00)

0.05 (0.01)

213

Olsenella sp._oral_taxon_807

0.04 (0.00)

0.04 (0.01)

0.04 (0.00)

0.05 (0.00)

214

Capnocytophaga sp._oral_taxon_323

0.04 (0.00)

0.03 (0.01)

0.05 (0.01)

0.05 (0.01)

215

Capnocytophaga sp._oral_taxon_903

0.04 (0.00)

0.03 (0.01)

0.04 (0.01)

0.05 (0.01)

216

Fretibacterium sp._oral_taxon_361

0.04 (0.01)

0.01 (0.00)

0.05 (0.02)

0.05 (0.02)

217

Leptotrichia sp._oral_taxon_219

0.04 (0.00)

0.05 (0.02)

0.04 (0.00)

0.04 (0.01)

218

Prevotella sp._oral_taxon_306

0.04 (0.01)

0.04 (0.02)

0.03 (0.01)

0.06 (0.01)

219

Atopobium sp._oral_taxon_199

0.04 (0.01)

0.04 (0.01)

0.04 (0.01)

0.03 (0.01)

220

Capnocytophaga sp._oral_taxon_324

0.04 (0.01)

0.03 (0.01)

0.04 (0.01)

0.05 (0.01)

221

Prevotella buccae

0.04 (0.00)

0.02 (0.00)

0.04 (0.01)

0.05 (0.01)

222

Prevotella baroniae

0.04 (0.00)

0.02 (0.01)

0.04 (0.01)

0.04 (0.01)

223

Lachnospiraceae_[G-8] sp._oral_taxon_500

0.04 (0.00)

0.04 (0.01)

0.04 (0.01)

0.04 (0.00)

224

Prevotella sp._oral_taxon_376

0.04 (0.00)

0.05 (0.01)

0.04 (0.01)

0.03 (0.01)

225

Porphyromonas sp._oral_taxon_278

0.04 (0.01)

0.03 (0.01)

0.04 (0.01)

0.04 (0.01)

226

Solobacterium moorei

0.04 (0.00)

0.04 (0.00)

0.04 (0.00)

0.04 (0.00)

227

Campylobacter curvus

0.03 (0.00)

0.05 (0.01)

0.03 (0.01)

0.03 (0.01)

228

Prevotella micans

0.03 (0.00)

0.03 (0.01)

0.03 (0.01)

0.04 (0.01)

229

Bacteroidaceae_[G-1] sp._oral_taxon_272

0.03 (0.00)

0.03 (0.01)

0.03 (0.00)

0.04 (0.01)

230

Streptococcus australis

0.03 (0.00)

0.03 (0.01)

0.03 (0.00)

0.04 (0.01)

231

Tannerella sp._oral_taxon_808

0.03 (0.00)

0.02 (0.00)

0.03 (0.00)

0.04 (0.01)

232

Bergeyella sp._oral_taxon_907

0.03 (0.00)

0.03 (0.01)

0.04 (0.01)

0.03 (0.00)

233

Prevotella multiformis

0.03 (0.01)

0.01 (0.00)

0.03 (0.01)

0.05 (0.02)

234

Fusobacterium sp._oral_taxon_370

0.03 (0.01)

0.02 (0.01)

0.04 (0.01)

0.03 (0.01)

235

Capnocytophaga sp._oral_taxon_380

0.03 (0.01)

0.03 (0.01)

0.04 (0.01)

0.03 (0.01)

236

Peptostreptococcaceae_[XI][G-1] [Eubacterium]_infi

0.03 (0.00)

0.03 (0.01)

0.03 (0.00)

0.04 (0.00)

237

Treponema medium

0.03 (0.00)

0.03 (0.01)

0.04 (0.01)

0.02 (0.01)

238

Lachnoanaerobaculum orale

0.03 (0.00)

0.04 (0.01)

0.02 (0.00)

0.03 (0.01)

239

Alloprevotella sp._oral_taxon_308

0.03 (0.00)

0.03 (0.00)

0.03 (0.00)

0.03 (0.01)

240

SR1_[G-1] sp._oral_taxon_874

0.03 (0.00)

0.03 (0.00)

0.03 (0.01)

0.02 (0.00)

241

Actinomyces israelii

0.03 (0.00)

0.03 (0.00)

0.03 (0.00)

0.03 (0.00)

242

Shuttleworthia satelles

0.03 (0.00)

0.02 (0.01)

0.03 (0.01)

0.04 (0.01)

243

Mycoplasma salivarium

0.03 (0.00)

0.02 (0.00)

0.03 (0.00)

0.03 (0.00)

244

Leptotrichia goodfellowii

0.03 (0.00)

0.04 (0.01)

0.03 (0.01)

0.02 (0.00)

245

Streptococcus sinensis

0.03 (0.00)

0.03 (0.01)

0.02 (0.00)

0.04 (0.01)

246

TM7_[G-3] sp._oral_taxon_351

0.03 (0.00)

0.02 (0.00)

0.03 (0.00)

0.03 (0.00)

247

Mitsuokella sp._oral_taxon_521

0.03 (0.01)

0.01 (0.01)

0.02 (0.01)

0.04 (0.02)

248

Selenomonas sp._oral_taxon_442

0.03 (0.01)

0.01 (0.00)

0.04 (0.01)

0.02 (0.01)

249

Actinomyces sp._oral_taxon_178

0.03 (0.00)

0.02 (0.00)

0.03 (0.00)

0.03 (0.00)

250

Johnsonella sp._oral_taxon_166

0.02 (0.00)

0.02 (0.01)

0.03 (0.00)

0.02 (0.00)

251

Lactobacillus gasseri

0.02 (0.01)

0.01 (0.00)

0.02 (0.01)

0.03 (0.01)

252

Treponema sp._oral_taxon_247

0.02 (0.01)

0.01 (0.01)

0.03 (0.01)

0.02 (0.01)

253

GN02_[G-2] sp._oral_taxon_873

0.02 (0.00)

0.03 (0.02)

0.02 (0.01)

0.02 (0.01)

254

Selenomonas sp._oral_taxon_937

0.02 (0.00)

0.01 (0.00)

0.02 (0.01)

0.02 (0.00)

255

Atopobium sp._oral_taxon_416

0.02 (0.01)

0.00 (0.00)

0.01 (0.01)

0.04 (0.02)

256

Sphingomonas echinoides

0.02 (0.00)

0.02 (0.01)

0.02 (0.00)

0.02 (0.01)

257

Butyrivibrio sp._oral_taxon_080

0.02 (0.00)

0.02 (0.01)

0.02 (0.01)

0.02 (0.00)

258

Treponema vincentii

0.02 (0.00)

0.02 (0.00)

0.03 (0.00)

0.01 (0.00)

259

Selenomonas sp._oral_taxon_149

0.02 (0.00)

0.01 (0.00)

0.02 (0.01)

0.02 (0.00)

260

Selenomonas sp._oral_taxon_478

0.02 (0.00)

0.01 (0.00)

0.01 (0.00)

0.02 (0.01)

261

Prevotella sp._oral_taxon_475

0.02 (0.00)

0.02 (0.01)

0.02 (0.00)

0.02 (0.01)

262

Pyramidobacter piscolens

0.01 (0.00)

0.01 (0.01)

0.00 (0.00)

0.01 (0.00)

263

Microbacterium flavescens

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

264

Brevundimonas diminuta

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

265

Sphingomonas sp._oral_taxon_006

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

266

Leptothrix sp._oral_taxon_025

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

267

Porphyrobacter tepidarius

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

0.00 (0.00)

aBacteria in the table are rank ordered according to their mean relative abundance (%) in the overall cohort

Dashed line inserted below the top 20 taxa

Table 6

Prevalence (present, absent) for each of 267 bacterial species identified, overall and by age categories

Rank Ordera

OTU Label

 

Age categories (years)

Overall

(N = 1219)

50–59

(N = 239)

60–69

(N = 554)

≥70

(N = 426)

%

%

%

%

1

Streptococcus oralis

100

100

100

100

1

Veillonella dispar

100

100

100

100

1

Veillonella parvula

100

100

100

100

4

Selenomonas sputigena

99.8

99.6

99.8

99.8

5

Fusobacterium nucleatum_subsp._vincentii

99.6

99.6

99.6

99.5

6

Fusobacterium nucleatum_subsp._animalis

99.3

99.6

99.3

99.3

6

Granulicatella adiacens

99.3

99.2

99.5

99.3

8

Streptococcus sanguinis

99.3

100

99.3

99.1

9

Rothia dentocariosa

99.2

99.2

99.3

99.1

10

Campylobacter gracilis

99.1

99.6

98.9

99.1

11

Selenomonas noxia

99.0

98.7

99.1

99.1

11

Streptococcus gordonii

99.0

98.7

98.9

99.3

13

Fusobacterium nucleatum_subsp._polymorphum

98.6

99.2

98.9

97.9

14

Fusobacterium sp._oral_taxon_203

98.4

98.7

98.0

98.8

14

Streptococcus cristatus

98.4

98.7

98.2

98.6

14

Fusobacterium naviforme

98.4

99.2

98.6

97.7

17

Actinomyces naeslundii

98.0

97.9

98.2

97.9

18

Corynebacterium matruchotii

97.5

96.7

97.3

98.1

19

Prevotella oris

97.2

97.5

97.3

96.9

20

Actinomyces oris

97.1

97.5

96.9

97.2

21

Streptococcus salivarius

97.0

96.7

96.8

97.7

21

Parvimonas micra

97.0

95.8

96.9

97.7

23

Haemophilus parainfluenzae

96.9

98.7

97.3

95.3

24

Streptococcus intermedius

96.8

97.9

95.5

97.9

25

Veillonella atypica

96.4

95.0

95.7

98.1

26

Rothia mucilaginosa

96.1

96.2

96.2

96.0

27

Dialister invisus

95.4

95.8

94.6

96.2

28

Campylobacter concisus

95.2

95.8

94.8

95.3

29

Capnocytophaga gingivalis

94.9

95.8

94.9

94.4

29

TM7_[G-1] sp._oral_taxon_346

94.9

95.0

96.0

93.4

31

Prevotella nigrescens

94.2

95.0

94.2

93.7

32

Kingella oralis

93.0

92.9

94.2

91.5

33

Bergeyella sp._oral_taxon_322

92.7

92.9

91.9

93.7

34

Gemella haemolysans

92.5

91.6

94.2

90.8

35

Actinomyces sp._oral_taxon_169

92.3

93.7

93.0

90.6

36

Actinomyces sp._oral_taxon_180

92.1

94.1

92.2

90.8

36

Eikenella corrodens

92.1

95.4

92.6

89.7

38

Prevotella melaninogenica

91.6

92.1

90.6

92.7

38

TM7_[G-1] sp._oral_taxon_349

91.6

92.9

92.4

89.7

40

Campylobacter showae

91.3

91.6

91.0

91.5

41

Actinomyces johnsonii

91.1

91.6

91.7

90.1

42

Capnocytophaga granulosa

90.8

89.5

92.4

89.4

43

Selenomonas sp._oral_taxon_136

90.7

89.1

90.4

92.0

44

Bacteroidales_[G-2] sp._oral_taxon_274

90.4

88.3

91.5

90.1

45

Selenomonas artemidis

90.3

90.4

90.4

90.1

46

Capnocytophaga leadbetteri

90.2

90.0

91.7

88.5

46

Actinomyces massiliensis

90.2

92.1

91.3

87.6

48

Fretibacterium sp._oral_taxon_360

90.0

91.2

90.4

88.7

49

Gemella morbillorum

89.8

89.5

90.3

89.4

50

Streptococcus sp._oral_taxon_074

89.3

87.0

91.0

88.3

51

Rothia aeria

89.2

90.0

91.9

85.2

52

Treponema socranskii

88.8

88.7

88.4

89.4

53

Leptotrichia hongkongensis

88.7

85.4

89.2

89.9

54

Streptococcus mutans

88.4

84.9

88.1

90.8

54

Cardiobacterium hominis

88.4

91.6

89.2

85.4

54

TM7_[G-1] sp._oral_taxon_952

88.4

90.0

90.3

85.0

57

Actinomyces gerencseriae

87.9

84.9

87.0

90.6

58

Leptotrichia wadei

87.7

86.6

87.0

89.2

59

Anaeroglobus geminatus

87.6

89.1

86.5

88.3

60

Streptococcus parasanguinis_II

87.4

87.4

84.3

91.5

61

Alloprevotella tannerae

87.3

90.0

85.6

88.0

62

Actinomyces sp._oral_taxon_171

87.2

88.7

87.4

86.2

62

Capnocytophaga sputigena

87.2

88.7

89.0

84.0

64

Fusobacterium nucleatum_subsp._nucleatum

86.8

90.8

86.5

85.0

65

Catonella morbi

86.6

87.0

87.2

85.7

66

Corynebacterium durum

85.6

88.7

86.8

82.2

66

Selenomonas infelix

85.6

88.7

85.6

83.8

68

Prevotella denticola

85.5

82.8

84.7

88.0

69

Prevotella sp._oral_taxon_317

85.2

88.3

83.6

85.4

70

Leptotrichia sp._oral_taxon_212

84.8

87.4

87.0

80.5

71

Porphyromonas sp._oral_taxon_279

84.5

83.7

85.7

83.3

72

Neisseria sicca

83.5

80.8

86.3

81.5

73

Gemella sanguinis

83.1

85.4

80.9

84.7

74

Peptostreptococcaceae_[XI][G-9] [Eubacterium]_brac

83.0

87.4

82.5

81.2

75

Tannerella forsythia

82.9

82.0

83.8

82.4

75

Neisseria flavescens

82.9

77.8

85.4

82.4

77

Prevotella sp._oral_taxon_300

82.5

80.8

81.4

85.0

78

Prevotella maculosa

82.3

80.8

81.4

84.3

79

Neisseria elongata

82.2

80.3

84.1

80.8

80

Selenomonas flueggei

82.0

79.9

82.9

81.9

81

Selenomonas sp._oral_taxon_892

81.8

85.4

83.6

77.5

82

Actinomyces israelii

81.7

79.9

80.9

83.8

83

Oribacterium sp._oral_taxon_078

81.4

78.2

80.1

84.7

84

Lachnoanaerobaculum saburreum

81.3

78.7

82.5

81.2

85

Megasphaera micronuciformis

81.1

79.1

78.5

85.4

85

Prevotella salivae

81.1

73.2

80.9

85.7

87

Streptococcus parasanguinis_I

80.6

80.3

78.2

84.0

88

Cardiobacterium valvarum

80.5

81.2

82.1

77.9

89

Prevotella oulorum

80.1

82.8

77.6

81.9

89

Veillonellaceae_[G-1] sp._oral_taxon_150

80.1

78.2

79.1

82.4

91

Leptotrichia sp._oral_taxon_417

79.7

74.5

80.3

81.7

92

Veillonella rogosae

79.6

82.4

82.7

73.9

93

Streptococcus anginosus

79.5

81.2

78.0

80.5

94

Veillonellaceae_[G-1] sp._oral_taxon_155

79.4

77.4

77.8

82.6

95

Fretibacterium fastidiosum

79.2

79.1

80.1

78.2

96

Lautropia mirabilis

78.2

82.8

78.9

74.6

97

Actinobaculum sp._oral_taxon_183

78.0

78.7

78.3

77.2

98

Fusobacterium periodonticum

77.7

74.9

82.1

73.5

99

Selenomonas sp._oral_taxon_919

77.2

84.1

75.6

75.4

100

Selenomonas sp._oral_taxon_137

76.8

80.3

76.9

74.6

101

Atopobium parvulum

76.5

76.2

73.8

80.3

101

Streptococcus lactarius

76.5

80.3

75.1

76.1

103

Kingella denitrificans

76.3

72.0

76.0

79.1

104

Capnocytophaga sp._oral_taxon_336

75.1

77.4

75.5

73.5

105

Lachnospiraceae_[G-3] sp._oral_taxon_100

73.7

77.0

73.6

72.1

106

Atopobium rimae

73.3

72.4

73.1

74.2

107

Streptococcus constellatus

73.0

72.8

71.7

74.9

108

Tannerella sp._oral_taxon_286

72.8

69.9

74.9

71.8

108

Selenomonas sp._oral_taxon_134

72.8

75.7

72.9

70.9

110

Leptotrichia buccalis

72.0

64.9

76.0

70.9

111

Selenomonas sp._oral_taxon_146

71.9

73.2

72.9

69.7

112

Leptotrichia sp._oral_taxon_215

71.8

75.3

72.4

69.0

113

Leptotrichia sp._oral_taxon_392

71.4

74.5

74.9

65.0

114

TM7_[G-5] sp._oral_taxon_356

71.2

74.5

72.2

68.1

115

Dialister pneumosintes

70.6

74.1

70.2

69.2

115

Prevotella sp._oral_taxon_472

70.6

71.5

75.3

64.1

117

Streptococcus sp._oral_taxon_056

70.6

69.0

73.3

68.1

118

Fretibacterium sp._oral_taxon_359

70.5

66.9

71.1

71.6

119

Solobacterium moorei

70.4

69.0

70.0

71.6

120

Abiotrophia defectiva

70.1

69.9

72.9

66.7

121

Lachnoanaerobaculum umeaense

69.3

69.9

70.2

67.8

122

Parvimonas sp._oral_taxon_393

69.2

69.9

70.2

67.4

123

Actinomyces meyeri

67.8

71.1

69.7

63.4

124

Centipeda periodontii

67.7

64.0

69.1

67.8

125

Leptotrichia shahii

67.6

72.4

66.6

66.2

126

Olsenella sp._oral_taxon_807

66.9

61.9

67.1

69.2

127

Actinobaculum sp._oral_taxon_848

66.3

64.9

66.1

67.4

128

Leptotrichia hofstadii

66.0

63.6

68.2

64.6

128

Neisseria oralis

66.0

66.1

69.0

62.2

128

Prevotella histicola

66.0

62.3

62.8

72.1

131

Actinomyces sp._oral_taxon_178

65.8

61.1

65.3

69.0

132

Stomatobaculum longum

65.7

62.3

63.7

70.2

132

TM7_[G-1] sp._oral_taxon_352

65.7

60.3

70.6

62.4

134

Capnocytophaga sp._oral_taxon_326

65.4

64.4

68.1

62.4

135

Prevotella oralis

64.5

63.6

65.2

64.1

136

Streptococcus sinensis

63.9

65.7

62.1

65.3

137

Alloprevotella sp._oral_taxon_308

63.5

68.6

61.9

62.7

138

Porphyromonas sp._oral_taxon_284

63.3

64.4

66.8

58.2

138

Prevotella pallens

63.3

63.2

61.7

65.5

140

Aggregatibacter sp._oral_taxon_458

63.2

65.7

65.3

58.9

141

Porphyromonas endodontalis

63.1

69.5

63.7

58.7

142

Prevotella saccharolytica

63.0

65.3

65.0

59.2

143

Selenomonas sp._oral_taxon_126

62.0

62.3

63.4

60.1

144

Lachnoanaerobaculum orale

61.1

63.2

58.5

63.4

145

Treponema maltophilum

61.0

59.0

62.3

60.3

146

Peptostreptococcaceae_[XI][G-7] [Eubacterium]_yuri

60.2

64.0

62.3

55.4

147

Veillonella denticariosi

60.1

56.5

60.8

61.3

148

Sphingomonas echinoides

59.8

64.9

61.7

54.5

149

Streptococcus australis

59.7

57.3

59.0

62.0

150

TM7_[G-1] sp._oral_taxon_348

59.6

57.7

63.4

55.9

151

TM7_[G-1] sp._oral_taxon_488

57.8

56.9

61.2

54.0

152

Ruminococcaceae_[G-1] sp._oral_taxon_075

56.9

58.2

59.7

52.6

153

Selenomonas sp._oral_taxon_936

56.8

58.2

56.3

56.8

154

Prevotella buccae

56.7

49.4

54.7

63.4

155

Leptotrichia sp._oral_taxon_225

56.4

60.3

58.7

51.4

155

Prevotella pleuritidis

56.4

55.2

59.4

53.3

157

Alloprevotella rava

56.2

57.7

56.9

54.5

158

Aggregatibacter aphrophilus

56.1

57.7

59.6

50.7

159

Treponema denticola

56.0

59.4

58.1

51.4

160

Peptostreptococcus stomatis

55.9

64.0

55.1

52.3

161

Pseudomonas fluorescens

55.5

53.6

57.0

54.5

162

Actinomyces sp._oral_taxon_170

55.2

60.3

57.0

50.0

163

Porphyromonas gingivalis

55.1

51.0

56.3

55.9

164

Haemophilus sp._oral_taxon_036

55.0

59.4

54.7

52.8

165

Johnsonella ignava

54.6

54.0

56.3

52.8

166

Porphyromonas catoniae

54.4

57.7

56.5

49.8

167

Peptostreptococcaceae_[XI][G-1] [Eubacterium]_infi

54.2

47.3

54.7

57.5

168

Prevotella sp._oral_taxon_292

53.8

49.4

54.3

55.6

169

Fretibacterium sp._oral_taxon_362

53.6

53.6

53.8

53.3

170

TM7_[G-1] sp._oral_taxon_347

53.2

58.2

54.3

49.1

171

Leptotrichia sp._oral_taxon_219

52.7

49.4

54.2

52.6

172

Aggregatibacter segnis

52.1

56.1

54.9

46.2

173

TM7_[G-3] sp._oral_taxon_351

51.9

45.6

55.4

50.9

174

Fusobacterium sp._oral_taxon_370

51.1

45.6

55.6

48.4

175

Prevotella sp._oral_taxon_313

50.5

53.1

46.4

54.2

176

Prevotella loescheii

50.4

52.3

54.5

43.9

177

Desulfobulbus sp._oral_taxon_041

50.3

48.1

50.9

50.7

178

Capnocytophaga sp._oral_taxon_864

49.1

51.9

52.0

43.9

179

Ottowia sp._oral_taxon_894

48.4

49.4

50.2

45.5

180

Microbacterium flavescens

48.0

50.2

49.5

44.8

181

Leptotrichia sp._oral_taxon_498

47.8

42.3

48.2

50.5

182

Granulicatella elegans

47.3

52.7

45.5

46.5

183

Filifactor alocis

46.8

50.2

46.8

44.8

184

Campylobacter curvus

46.2

45.6

46.4

46.2

185

Mycoplasma salivarium

45.0

47.7

45.3

43.2

186

Capnocytophaga sp._oral_taxon_338

44.8

42.7

44.4

46.5

187

Capnocytophaga sp._oral_taxon_902

44.3

43.1

46.6

42.0

188

Treponema sp._oral_taxon_231

43.6

51.5

45.3

37.1

189

Tannerella sp._oral_taxon_808

43.1

39.3

45.7

41.8

190

Prevotella intermedia

42.8

40.2

43.3

43.7

191

TM7_[G-6] sp._oral_taxon_870

42.7

43.9

44.2

39.9

192

Mitsuokella sp._oral_taxon_131

42.2

35.6

41.0

47.7

193

Haemophilus haemolyticus

42.0

47.3

41.3

39.9

194

Prevotella veroralis

41.7

44.4

40.8

41.3

195

Veillonellaceae_[G-1] sp._oral_taxon_129

40.9

37.7

40.8

43.0

195

Aggregatibacter paraphrophilus

40.9

45.2

42.2

36.6

197

Pseudoramibacter alactolyticus

40.9

33.5

41.5

44.1

198

Bergeyella sp._oral_taxon_907

40.6

39.7

42.8

38.3

199

Bifidobacterium dentium

40.5

33.9

37.9

47.7

199

TM7_[G-1] sp._oral_taxon_869

40.5

41.8

41.5

38.5

201

Prevotella sp._oral_taxon_306

40.3

36.0

39.5

43.7

202

Prevotella dentalis

39.3

40.2

36.5

42.5

203

Shuttleworthia satelles

39.2

34.7

37.5

43.9

204

Veillonella sp._oral_taxon_780

39.1

40.6

42.4

34.0

205

Capnocytophaga sp._oral_taxon_412

38.7

38.9

41.5

35.0

206

Neisseria subflava

38.6

39.3

37.4

39.7

206

Scardovia wiggsiae

38.6

37.2

37.7

40.4

208

Leptotrichia sp._oral_taxon_223

37.8

42.3

36.5

37.1

209

Peptostreptococcaceae_[XI][G-6] [Eubacterium]_noda

37.2

35.6

37.0

38.5

209

Selenomonas sp._oral_taxon_937

37.2

36.4

35.2

40.1

211

Bacteroidetes_[G-5] sp._oral_taxon_511

36.8

41.0

37.2

33.8

212

Capnocytophaga sp._oral_taxon_323

36.7

36.0

37.4

36.2

213

Selenomonas sp._oral_taxon_149

36.4

30.5

33.8

43.2

213

Selenomonas sp._oral_taxon_442

36.4

30.1

37.5

38.5

215

SR1_[G-1] sp._oral_taxon_874

36.3

39.3

40.3

29.6

216

Porphyromonas sp._oral_taxon_275

36.0

36.4

37.7

33.6

217

Selenomonas sp._oral_taxon_478

35.9

31.4

38.4

35.2

218

Alloprevotella sp._oral_taxon_473

35.8

39.7

36.8

32.4

219

Neisseria bacilliformis

35.5

35.1

35.4

35.9

220

Capnocytophaga sp._oral_taxon_324

35.4

32.6

38.1

33.3

221

Veillonellaceae_[G-1] sp._oral_taxon_145

35.2

35.1

36.1

34.0

222

Atopobium sp._oral_taxon_199

34.9

36.0

36.1

32.6

223

Lachnospiraceae_[G-8] sp._oral_taxon_500

34.8

33.1

35.7

34.5

224

TM7_[G-2] sp._oral_taxon_350

34.6

34.7

34.7

34.5

225

Bacteroidaceae_[G-1] sp._oral_taxon_272

33.1

26.8

33.9

35.7

225

Capnocytophaga sp._oral_taxon_903

33.1

31.8

36.1

30.0

225

Selenomonas dianae

33.1

28.9

35.0

32.9

228

Prevotella baroniae

33.0

32.2

33.4

32.9

229

Leptotrichia goodfellowii

32.2

37.2

34.1

27.0

230

Prevotella micans

31.4

29.3

32.7

31.0

231

Porphyromonas sp._oral_taxon_278

31.0

31.8

31.9

29.3

232

Prevotella sp._oral_taxon_314

30.8

30.1

31.4

30.5

233

Haemophilus parahaemolyticus

30.3

37.2

31.8

24.4

234

Anaerolineae_[G-1] sp._oral_taxon_439

30.2

25.5

30.0

33.1

235

Selenomonas sp._oral_taxon_133

30.1

28.9

30.5

30.3

236

Treponema lecithinolyticum

29.5

30.1

31.2

26.8

237

Peptostreptococcaceae_[XI][G-5] [Eubacterium]_saph

28.3

22.2

31.4

27.7

238

Treponema sp._oral_taxon_237

27.0

32.2

28.9

21.6

239

Neisseria pharyngis

25.8

25.1

25.5

26.8

240

Leptotrichia sp._oral_taxon_879

25.4

25.9

25.6

24.9

241

Brevundimonas diminuta

25.3

27.6

25.8

23.2

242

Bradyrhizobium elkanii

24.9

26.4

22.7

26.8

242

Capnocytophaga sp._oral_taxon_332

24.9

29.7

26.2

20.4

244

Megasphaera sp._oral_taxon_123

24.5

32.2

24.2

20.7

245

Capnocytophaga sp._oral_taxon_380

22.2

20.5

24.9

19.7

246

Treponema vincentii

22.0

23.0

23.5

19.5

247

Prevotella sp._oral_taxon_376

21.4

26.8

23.5

15.7

248

Prevotella sp._oral_taxon_526

21.1

21.8

21.7

20.0

249

Aggregatibacter sp._oral_taxon_513

20.2

21.8

23.1

15.5

250

Lactobacillus gasseri

19.9

18.0

17.9

23.7

251

Fretibacterium sp._oral_taxon_358

19.3

16.7

19.3

20.7

252

Mitsuokella sp._oral_taxon_521

18.7

18.4

19.9

17.4

253

Fretibacterium sp._oral_taxon_361

18.5

15.5

19.1

19.2

254

Prevotella sp._oral_taxon_475

18.2

19.2

20.0

15.3

255

Treponema medium

18.1

16.3

19.5

17.4

256

Johnsonella sp._oral_taxon_166

16.7

12.6

18.6

16.7

257

Streptococcus sobrinus

15.9

13.8

14.4

19.0

258

Prevotella multiformis

15.5

16.3

15.5

15.0

259

Butyrivibrio sp._oral_taxon_080

14.5

15.1

15.9

12.4

260

GN02_[G-2] sp._oral_taxon_873

13.7

10.9

15.0

13.6

261

Aggregatibacter actinomycetemcomitans

12.3

12.1

11.4

13.6

262

Leptothrix sp._oral_taxon_025

10.9

13.4

11.4

8.9

263

Atopobium sp._oral_taxon_416

8.7

5.4

8.5

10.8

264

Sphingomonas sp._oral_taxon_006

7.2

5.9

7.9

7.0

265

Porphyrobacter tepidarius

6.9

7.1

6.1

7.7

266

Treponema sp._oral_taxon_247

4.8

6.3

4.5

4.2

267

Pyramidobacter piscolens

4.0

2.9

3.8

4.9

aBacteria in the table are rank ordered according to their prevalence in the overall cohort

Dashed line inserted below top 20 taxa

Discussion

The objective of the present study was to characterize, using high throughput sequencing of the 16S rRNA bacterial gene, the subgingival microbiome in relation to age among community-dwelling postmenopausal women, aged 53–81 years, whose selection into the study was not conditioned on presence or severity of periodontitis. We identified 267 taxa, of which 55% had previously been named within the HOMD database. The remaining previously unnamed OTUs could potentially identify novel microbiota residing in human subgingival biofilm, new discovery that could have important implications to periodontal microbiology [17, 34, 35]. The majority of taxa identified in our study fell within the four major human bacterial phyla (Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria) determined in the HMP [36] and by others [3, 23] including the oral microbiome [21, 22, 37, 38, 39]. As in other studies on the oral microbiome [21, 22, 38, 39, 40, 41], the most abundant phyla in our study were Firmicutes, Bacteroidetes, Fusobacteria and Proteobacteria, accounting for 46, 17, 14, and 9%, respectively, of the 265 taxa identified. The Firmicutes-to-Bacteroidetes ratio has been suggested as a possible indicator of the overall status of a microbial habitat in aging humans [6]. Previous studies on the gut microbiome have shown a lower ratio in older compared with younger individuals [42, 43]. In contrast, we observed a tendency toward higher Firmicutes-to-Bacteroidetes ratios across incremental age groups. In so much as some of the most virulent and well established periodontal pathogens (e.g., P. gingivalis, T. forsythia, T. denticola) reside in the phylum Bacteroides, whereas bacteria associated with a healthy periodontium (S. sanguis, oralis) reside in the phylum Firmicutes, a higher F-B ratio in the present cohort of aging women might be expected given the relatively small mean probing pocket depth (2.2 mm) overall, and lack of difference in this clinical measure of periodontitis across age groups. Whether the F-B ratio has similar relevance in the oral microbiome as has been reported previously for the gut microbiome requires further investigation.

The most abundant genus in our cohort was Veillonella, followed by Streptococcus, Fusobacterium, and Prevotella, with little variation in the distribution across age categories. Previous studies using targeted methods for measuring oral microbiota found substantially elevated abundance of Actinomyces and Fusobacterium genera in older adults [17, 38], which was not the case in our study (Actinomyces, overall: 1%, 70–79 years: 2%; Fusobacterium, overall: 11%, 70–79 years 10%) when using untargeted high-throughput sequencing. Other studies that measured the oral microbiome using 16S rRNA sequencing have reported the distribution of genera. Among community-dwelling adults (mean age 83; 61% women), analysis of salivary microbiome revealed Prevotella (22%) was most abundant, followed by Neisseria (12%), Veillonella (10%), and Streptococcus (8%) [22]. In another study on the salivary microbiome in Mexican American women, aged 50 and older, Hoffman et al. [21] reported that Streptococcus was most abundant (37%), followed by Prevotella (11%), Haemophilus (10%), and Veillonella (6%). Among Alaskan adults, aged 20–40 years, Streptococcus (28%) and Prevotella (27%) were by far most abundant, followed by Rothia (11%) and Veillonella (8%) [41]. Variation of microbial genera with age was not reported in these previous studies. Notwithstanding, there does appear to be some consistency across studies using culture-independent sequencing methods, including ours, in that Streptococcus, Prevotella, and Veillonella are abundant microbial genera commonly observed in the adult human oral microbiome.

Our primary analysis on microbial species composition and variation with age was based on CLR transformed OTUs taking into account the complex compositional structure of microbiome data [32]. The top 20 most abundant bacterial species had CLR means from 3.85 to 8.25, indicating these species were 14- to 304-fold (i.e., 23.85 to 28.25) more abundant than the overall composition mean (Table 3). V. dispar, S. oralis, and V. parvula were the top three most abundant species, each with CLR means > 7. V. dispar and parvula are gram-negative anaerobic bacteria commonly found in the human oral cavity [44], and have been associated with caries and periodontitis [34]. Evidence suggests V. parvula synergizes with Lachnoanaerobaculum (Eubacterium) saburreum, and the energy it produces, as a critical part of human subgingival biofilm formation [45]. L. saburreum was found at a relatively small, but elevated, abundance in our cohort (mean CLR, 1.07). Both bacterial species were positively correlated with age in our study, with a stronger correlation for V. parvula (r = 0.10) compared with L. saburreum (r = 0.04). S. oralis, in contrast, tends to be abundant in soft tissues of healthy periodontium [34], and as such was an original component in Socransky’s “yellow complex” defined using the checkerboard DNA-DNA hybridization method. S. oralis abundance has been shown to decline in the setting of experimental subgingival biofilm growth [34], which suggests it might be a key bacterium involved with the shift from a healthy to disease subgingival microbial ecology leading to periodontitis. The correlations with age for V. parvula (r = 0.10) and S. oralis (r = − 0.10) observed in the present study suggest that age could be a potential host factor contributing to susceptibility for untoward shifts in the human subgingival microbial ecology. Chronological age, per se, however, may not be the biologically relevant effector of shifts in microbial ecology. Rather, the tendency of aging to be associated with chronic immune function decline and upregulated proinflammatory signaling [8], referred to as “inflamm-aging” by Franceshi and coworkers [46] is likely a culpable perturbation of colonizing microbiota. Consistent with this hypothesis are results from studies of experimentally induced gingivitis, which demonstrated markedly greater amounts and severity of biofilm development in older than younger adults, despite no obvious differences in microbial compositional characteristics of the biofilm between age groups [17].

In the present study, 12 bacterial species differed significantly across age groups (Fig. 5). The largest difference in bacteria elevated in older adults was for B. dentium (phylum Actinobacteria), an anaerobe that has strong adhesion capacity, tolerates highly acidic conditions, and has been associated with human dental caries [47], but also with suppression of P. gingivalis, a virulent periodontitis pathogen [48]. This might partially explain why P. gingivalis was in relatively low abundance in our cohort of older women. Anaeroglobus geminatus (phylum Firmicutes) also demonstrated a rather large elevation in older compared with younger adults in our cohort. This bacterium has an identified role in perturbing a shift in the subgingival microbial ecology that favors development of periodontitis [49]. There was no difference in mean pocket depth measures among age groups in our cohort of older women, among whom prevalence of major risk factors for periodontitis, smoking and diabetes, also were low. However, it is conceivable that higher abundance of B. dentium and A. geminatus in the older age group could be reflective of an ongoing subgingival microbial community shift that leads to increased susceptibility to periodontitis progression in these women over time. Longitudinal analyses are required to confirm this hypothesis.

S. sanguinis and Corynebacterium durum showed the largest differences in bacteria between age groups among those elevated in younger women (Fig. 5). S. sanguinis (phylum Firmicutes) is a gram-positive anaerobe that is abundant in healthy periodontium [34] and plays a role in modifying the environment on oral surfaces such as to suppress growth of other Streptococci bacteria involved with oral diseases, such as S. mutans which is a causal agent in human carries [50]. S. sanguinis also might play a role in the shift of subgingival microbiota from a healthy to a disease ecology, serving as an adhesion site for virulent periodontal pathogens, such as P. gingivalis and F. nucleatum [50], each of which were in relatively low abundance in the present study. The role that C. durum (phylum Actinobacteria), also a gram-positive bacterium, might have in the subginigival microbial ecology is not entirely clear. Elevations of this bacterium originally was identified in bronchial wash solution and implicated in maintaining a healthy respiratory tract [51] and later, it’s reduction in saliva was associated with halitosis [52] and celiac disease [53]. Given it’s propensity to produce acid from available sugar compounds in saliva [54], and perhaps in other oral fluids including the gingival crevice, it is possible that this bacterium has a role in establishing or maintaining pH of the gingival pocket at a level commensurate with survival of other bacteria associated with periodontal health, such as S. sanguinis.

The vast majority of studies using untargeted high-throughput sequencing methods of the oral microbiome have reported measures of relative abundance or prevalence when describing microbial composition. Our primary measure for analysis of microbiota abundance in was the centered log-transformed ratio (CLR) OTU, as recommended by Gloor and coworkers [32]. While the basic cross-sectional findings of the present study were generally consistent when based on mean CLR OTUs, relative abundance, and prevalence, we believe that the CLR approach is the method of choice. Compositional data are vectors of non-negative numbers that sum to a fixed value, a constraint that can lead to spurious correlations. Subsequent work by Aitchison and colleagues yielded a set of log-ratio transformations that alleviate the sum-constraint burden, provide a consistent variance-covariance structure, and ensure that statistical results show consistency over subcompositions and OTU permutations [32, 55]. Subcompositional consistency, in particular, is necessary for the fundamental scientific concept of reproducibility across studies. The application of methods which ignore the compositional structure of microbiome data, like simple proportions (e.g., relative abundance, prevalent, or rarefaction) can lead to false positive associations and inferences [32]. In addition, the CLR transformation does not reduce the dimensionality of the dataset, maintaining the correspondence between transformed variables and OTUs, and easing the interpretation of conventional statistical tests, such as bivariate correlations and analysis of variance. Given the recent growth in microbiome research, the plethora of published studies that used different analytic methods, and the potential impact that continued investigation of the human microbiome could have on future understanding of disease etiology and therapeutics [24], the need for standardization of methods for analyzing and reporting microbiome data is paramount.

The present study has both strengths and limitations that need be considered when interpreting and generalizing its findings. Strengths include the large sample size of community-dwelling older postmenopausal women whose selection into the study was not conditioned on periodontitis presence or severity. Of the published studies reporting on the oral microbiome in older adults, the vast majority included relatively small sample sizes (e.g., < 100) and individuals that were selected to have either periodontal health or disease, often recruited from dental or other healthcare settings [17, 18, 22, 37, 40, 56]. Understanding the epidemiology of oral microbiota composition and its association with host characteristics in a more general community setting is a critical foundational step for evaluating associations between oral microbiome and both oral and systemic disease, as well as response to therapeutic intervention [24]. Previous oral microbiome studies on older adults relied largely on targeted low-throughput methods for characterizing oral microbiota [17, 18, 38, 56]. The limitations of these methods have been discussed elsewhere [17, 57]. Only recently have studies, including ours, utilized state-of-the science untargeted high-throughput next generation sequencing methods to investigate the oral microbiome in adults in middle- and older ages [21, 22, 23, 39, 40, 41]. This not only allows for greater sensitivity in characterizing the complexity of oral microbial communities, but also for potential discovery of new previously unidentified microbiota, which is essential to deeper understanding of the oral microbiome [17, 35]. Weaknesses of the present study include its cross-sectional design, which precludes temporal understanding of the relationship between aging and formation of the observed oral microbiome. The cross-sectional nature of our results precludes causal inferences regarding the relationship between age and the subgingival microbial composition and diversity. Using means to describe complex data, such as the subgingival microbiome, is helpful for descriptive purposes and ease of understanding, however they do not provide insight on between-subject variability nor do they allow for understanding of shifts between healthy and disease ecologies [34]. Prospective studies are needed using statistical methods appropriate for quantifying changes in microbiota between groups differing on host characteristics, such as aging or periodontal disease onset and progression, or in response to therapeutic intervention. The present cross-sectional observations, such as the significant differences in CLR mean OTUs between older and younger women (Fig. 5), could inform development of hypotheses for testing in a prospective study design. Lastly, we were not able to determine the functional attributes of the particularly abundant or sparse microbiota identified in our older cohort of women, nor of the bacterium that differed in abundance between older and younger women. It is becoming clearer that the functions determined by the genes expressed by microbiota are likely more influential on health or disease states than is the microbial composition [1, 15, 17]. Because aging is a non-modifiable host characteristic intimately involved with both structural and functional changes in the human body over the adult lifespan, the relationship between age and microbial function is of high interest [7].

Conclusion

We conclude that in a large cross-sectional analysis on the subgingival microbiome in postmenopausal women, aged 53–81 years, who were not selected on the basis of periodontitis status, a diverse subgingival microbiome was present and several bacterial species were correlated with age across the age range studied. Twelve microbiota were identified that differed significantly in abundance between women aged 50–59 versus 70 and older. Prospective data are needed to characterize the temporal relation between aging and shifts or stability in the abundance and pattern of subgingival microbiota observed herein to better elucidate the role, if any, that aging has on the oral microbiome. Age alone, however, does not determine the human subgingival microbiome. Other factors, including senescence of tissues and functions, side effects of medication use, status of the gingiva and dentition, systemic diseases, oral hygiene and behavioral habits, are thought to influence the microbiome. The extensive cross-sectional observations reported here provide a starting point and direction to define a targeted subset of bacteria that appear be related with age for further analysis in which issues such as confounding or interaction with the above and other factors can be evaluated with greater statistical efficiency involving fewer tests to correct for false discovery. This will be the focus of a forthcoming manuscript from our longitudinal cohort. Additional understanding about the functions of bacteria that differ with age in later life could identify intervention targets for enhanced oral health and, possibly control of other diseases.

Notes

Acknowledgements

Not applicable.

Authors’ contributions

Conception, design, and acquisition of data and biologic samples in the original studies (JWW, RJG). Microbiome laboratory (MJB, YS, MT, DIM). Data analysis and interpretation (LL, DIM, KMH, CAA, MJL, MJB, WZ, YS, JWW, RJG). Manuscript drafting and editing (MJL, KMH, CAA, DIM, JWW, RJG, YS, MJB, WZ, LL, HB, AEM). Final Approval of manuscript (MJL, RJG, MJB, DIM, LL, KMH, CAA, WZ, YS, MT, HB, AEM, JWW). Agreed to be accountable for all aspects of the work ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved (MJL, JWW).

Funding

National Heart, Lung, and Blood Institute contract N01WH32122; National Institute for Dental and Craniofacial Research Grants: DE13505, DE4898, DE022654, and DE024523; National Institute of Allergy and Infectious Diseases R01Al125982, U.S. Army Reserve Medical Corps Grant: DAMD17–96-1-6319; Feasibility Study Award (AS382) from the Women’s Health Initiative Program. Decisions concerning design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, and approval of the manuscript, and the decision to submit the manuscript for publication resided with committees comprising WHI investigators that included NHLBI and NIDCR representatives. The contents of the manuscript are solely the responsibility of the authors.

Ethics approval and consent to participate

Participants provided written informed consent for all components of the studies, which were conducted in accord with the Helsinki Declaration on human subjects research. Experimental protocols for the WHI study, the OsteoPerio study, and microbiome study detailed in this paper were approved by the Institutional Review Board at the University at Buffalo.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Copyright information

© The Author(s). 2019

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • Michael J. LaMonte
    • 1
    Email author
  • Robert J. Genco
    • 2
  • Michael J. Buck
    • 3
  • Daniel I. McSkimming
    • 4
  • Lu Li
    • 5
  • Kathleen M. Hovey
    • 1
  • Christopher A. Andrews
    • 6
  • Wei Zheng
    • 5
  • Yijun Sun
    • 5
  • Amy E. Millen
    • 1
  • Maria Tsompana
    • 3
  • Hailey R. Banack
    • 1
  • Jean Wactawski-Wende
    • 1
  1. 1.Department of Epidemiology and Environmental Health, School of Public Health and Health ProfessionsUniversity at BuffaloBuffaloUSA
  2. 2.Department of Oral Biology, School of Dental Medicine, UB Microbiome CenterUniversity at BuffaloBuffaloUSA
  3. 3.Department of Biochemistry, School of Medicine and Biomedical Sciences, NY State Center of Excellence in Bioinformatics and Life SciencesUniversity at BuffaloBuffaloUSA
  4. 4.Genome, Environment, and Microbiome Center of ExcellenceUniversity at BuffaloBuffaloUSA
  5. 5.Department of Microbiology and Immunology and Department of Computer and Engineering Science, NY State Center of Excellence in Bioinformatics and Life SciencesUniversity at BuffaloBuffaloUSA
  6. 6.Department of Ophthalmology, School of MedicineUniversity of MichiganAnn ArborUSA

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