Digestive Diseases and Sciences

, Volume 63, Issue 6, pp 1525–1531 | Cite as

Fecal Microbiome Among Nursing Home Residents with Advanced Dementia and Clostridium difficile

  • Rafael Araos
  • Nikolaos Andreatos
  • Juan Ugalde
  • Susan Mitchell
  • Eleftherios Mylonakis
  • Erika M. C. D’Agata
Original Article



Patients colonized with toxinogenic strains of Clostridium difficile have an increased risk of subsequent infection. Given the potential role of the gut microbiome in increasing the risk of C. difficile colonization, we assessed the diversity and composition of the gut microbiota among long-term care facility (LTCF) residents with advanced dementia colonized with C. difficile.


Retrospective analysis of rectal samples collected during a prospective observational study.


Thirty-five nursing homes in Boston, Massachusetts.


Eighty-seven LTCF residents with advanced dementia.


Operational taxonomic units were identified using 16S rRNA sequencing. Samples positive for C. difficile were matched to negative controls in a 1:3 ratio and assessed for differences in alpha diversity, beta diversity, and differentially abundant features.


Clostridium difficile sequence variants were identified among 7/87 (8.04%) residents. No patient had evidence of C. difficile infection. Demographic characteristics and antimicrobial exposure were similar between the seven cases and 21 controls. The overall biodiversity among cases and controls was reduced with a median Shannon index of 3.2 (interquartile range 2.7–3.9), with no statistically significant differences between groups. The bacterial community structure was significantly different among residents with C. difficile colonization versus those without and included a predominance of Akkermansia spp., Dermabacter spp., Romboutsia spp., Meiothermus spp., Peptoclostridium spp., and Ruminococcaceae UGC 009.


LTCF residents with advanced dementia have substantial dysbiosis of their gut microbiome. Specific taxa characterized C. difficile colonization status.


Microbiome Advanced dementia Colonization Clostridium difficile 


Author’s contribution

Dr. D’Agata and Araos contributed to the study concept and design, acquisition of subjects, and collection of the relevant data. Dr. Araos, Ugalde, and D’Agata performed the data analysis. All authors contributed to data interpretation and collaborated on the drafting and revision of the manuscript. Dr. Araos is the guarantor and takes responsibility for the integrity of the data and the accuracy of the data analysis.


This work has been supported by the National Institute of Allergy and Infectious Diseases (K24 AI119158 [EMCD]), the Centers for Disease Control and Prevention’s investments to combat antibiotic resistance under Award Number 200-2016-91939 (EMCD and RA), NIH-NIA R01 AG032982 (SM, EMCD), and NIH-NIA K24AG033640 (SM).

Compliance with ethical standards

Conflict of interest

Juan Ugalde is an employee of uBiome Inc and has received stock options as well as other compensation.


  1. 1.
    Clostridium difficile infection in 2015. Centers for Disease Control and Prevention (CDC). Available at: Accessed July 3, 2017.
  2. 2.
    Antimicrobial resistance. Centers for Disease Control and Prevention (CDC). Available at: Accessed July 3, 2017.
  3. 3.
    Ziakas PD, Joyce N, Zacharioudakis IM, et al. Prevalence and impact of Clostridium difficile infection in elderly residents of long-term care facilities, 2011: a nationwide study. Medicine (Baltimore). 2016;95:e4187.CrossRefGoogle Scholar
  4. 4.
    Karanika S, Grigoras C, Flokas ME, et al. The attributable burden of Clostridium difficile infection to long-term care facilities stay: a Clinical Study. J Am Geriatr Soc. 2017;65:1733–1740.CrossRefPubMedGoogle Scholar
  5. 5.
    Ziakas PD, Zacharioudakis IM, Zervou FN, et al. Asymptomatic carriers of toxigenic C. difficile in long-term care facilities: a meta-analysis of prevalence and risk factors. PLoS ONE. 2015;10:e0117195.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Vincent C, Manges AR. Antimicrobial use, human gut microbiota and Clostridium difficile colonization and infection. Antibiotics (Basel). 2015;4:230–253.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Theriot CM, Young VB. Interactions between the gastrointestinal microbiome and Clostridium difficile. Annu Rev Microbiol. 2015;69:445–461.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Manges AR, Labbe A, Loo VG, et al. Comparative metagenomic study of alterations to the intestinal microbiota and risk of nosocomial Clostridum difficile-associated disease. J Infect Dis. 2010;202:1877–1884.CrossRefPubMedGoogle Scholar
  9. 9.
    Vincent C, Stephens DA, Loo VG, et al. Reductions in intestinal Clostridiales precede the development of nosocomial Clostridium difficile infection. Microbiome. 2013;1:18.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Girotra M, Garg S, Anand R, et al. Fecal microbiota transplantation for recurrent Clostridium difficile infection in the elderly: long-Term outcomes and microbiota changes. Dig Dis Sci. 2016;61:3007–3015.CrossRefPubMedGoogle Scholar
  11. 11.
    Seekatz AM, Aas J, Gessert CE, et al. Recovery of the gut microbiome following fecal microbiota transplantation. MBio. 2014;5:e00893-00814.CrossRefGoogle Scholar
  12. 12.
    Zacharioudakis IM, Zervou FN, Pliakos EE, et al. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis. Am J Gastroenterol. 2015;110:381–390. (quiz 391).CrossRefPubMedGoogle Scholar
  13. 13.
    Mitchell SL, Shaffer ML, Kiely DK, et al. The study of pathogen resistance and antimicrobial use in dementia: study design and methodology. Arch Gerontol Geriatr. 2013;56:16–22.CrossRefPubMedGoogle Scholar
  14. 14.
    Mitchell SL, Shaffer ML, Loeb MB, et al. Infection management and multidrug-resistant organisms in nursing home residents with advanced dementia. JAMA Intern Med. 2014;174:1660–1667.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Volicer L, Hurley AC, Lathi DC, et al. Measurement of severity in advanced Alzheimer’s disease. J Gerontol. 1994;49:M223–M226.CrossRefPubMedGoogle Scholar
  16. 16.
    Albert M, Cohen C. The Test for Severe Impairment: an instrument for the assessment of patients with severe cognitive dysfunction. J Am Geriatr Soc. 1992;40:449–453.CrossRefPubMedGoogle Scholar
  17. 17.
    Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–336.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Iizumi T, Taniguchi T, Yamazaki W, et al. Effect of antibiotic pre-treatment and pathogen challenge on the intestinal microbiota in mice. Gut Pathog. 2016;8:60.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Callahan BJ, McMurdie PJ, Rosen MJ, et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581–583.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    McMurdie PJ, Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE. 2013;8:e61217.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Mitchell SL. Advanced dementia. N Engl J Med. 2015;373:1276–1277.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178–184.CrossRefPubMedGoogle Scholar
  24. 24.
    Lewis BB, Pamer EG. Microbiota-based therapies for Clostridium difficile and antibiotic-resistant enteric infections. Annu Rev Microbiol. 2017;71:157–178.CrossRefPubMedGoogle Scholar
  25. 25.
    Antharam VC, Li EC, Ishmael A, et al. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013;51:2884–2892.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Kim S, Covington A, Pamer EG. The intestinal microbiota: antibiotics, colonization resistance, and enteric pathogens. Immunol Rev. 2017;279:90–105.CrossRefPubMedGoogle Scholar
  27. 27.
    D’Agata E, Mitchell SL. Patterns of antimicrobial use among nursing home residents with advanced dementia. Arch Intern Med. 2008;168:357–362.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lee YJ, Arguello ES, Jenq RR, et al. Protective factors in the intestinal microbiome against Clostridium difficile infection in recipients of allogeneic hematopoietic stem cell transplantation. J Infect Dis. 2017;215:1117–1123.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lawley TD, Walker AW. Intestinal colonization resistance. Immunology. 2013;138:1–11.CrossRefPubMedGoogle Scholar
  30. 30.
    Schubert AM, Rogers MA, Ring C, et al. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. MBio. 2014;5:e01021-01014.CrossRefGoogle Scholar
  31. 31.
    Zhang L, Dong D, Jiang C, et al. Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization. Anaerobe. 2015;34:1–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Milani C, Ticinesi A, Gerritsen J, et al. Gut microbiota composition and Clostridium difficile infection in hospitalized elderly individuals: a metagenomic study. Sci Rep. 2016;6:25945.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Rea MC, O’Sullivan O, Shanahan F, et al. Clostridium difficile carriage in elderly subjects and associated changes in the intestinal microbiota. J Clin Microbiol. 2012;50:867–875.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Chang JY, Antonopoulos DA, Kalra A, et al. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008;197:435–438.CrossRefPubMedGoogle Scholar
  35. 35.
    Bassis CM, Moore NM, Lolans K, et al. Comparison of stool versus rectal swab samples and storage conditions on bacterial community profiles. BMC Microbiol. 2017;17:78.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Budding AE, Grasman ME, Eck A, et al. Rectal swabs for analysis of the intestinal microbiota. PLoS ONE. 2014;9:e101344.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Rafael Araos
    • 1
  • Nikolaos Andreatos
    • 2
  • Juan Ugalde
    • 3
    • 4
  • Susan Mitchell
    • 5
  • Eleftherios Mylonakis
    • 2
  • Erika M. C. D’Agata
    • 2
  1. 1.Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clínica AlemanaUniversidad del DesarrolloSantiagoChile
  2. 2.Infectious Diseases Division, Rhode Island HospitalWarren Alpert Medical School of Brown UniversityProvidenceUSA
  3. 3.uBiome, IncSan FranciscoUSA
  4. 4.Centro de Bioinformatica y Biología Integrativa, Facultad de Ciencias BiológicasUniversidad Andrés BelloSantiagoChile
  5. 5.Hebrew SeniorLife Institute for Aging ResearchBostonUSA

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