Human gut microbes are susceptible to antimicrobial food additives in vitro
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The aim of this work was to test the hypothesis that antimicrobial food additives may alter the composition of human gut microbiota by selectively suppressing the growth of susceptible gut microbes. To explore the influence of antimicrobial food additives on the composition of the human gut microbiota, we examined the susceptibility of both aerobic and anaerobic gut bacteria to sodium benzoate, sodium nitrite, and potassium sorbate, and their combinations, using a broth microdilution method. The tested bacteria exhibited a wide range of susceptibilities to food additives. For example, the most susceptible strain, Bacteroides coprocola, was almost 580 times more susceptible to sodium nitrite than the most resistant strain, Enterococcus faecalis. However, most importantly, we found that gut microbes with known anti-inflammatory properties, such as Clostridium tyrobutyricum or Lactobacillus paracasei, were significantly more susceptible to additives than microbes with known proinflammatory or colitogenic properties, such as Bacteroides thetaiotaomicron or Enterococcus faecalis. Our data show that some human gut microbes are highly susceptible to antimicrobial food additives. We speculate that permanent exposure of human gut microbiota to even low levels of additives may modify the composition and function of gut microbiota and thus influence the host’s immune system. Whether the effect of additive-modified gut microbiota on the human immune system could explain, at least in part, the increasing incidence of allergies and autoimmune diseases remains to be shown.
KeywordsGut microbiota Autoimmune diseases Dysbiosis Mucosal immunology Food additives Chou-Talalay method
We would like to thank Radka Stribrna and Jarmila Jarkovska for their invaluable technical support and James Rizzo for editing and proofreading the manuscript.
This study was supported by the Charles University Grant Agency (No. 906613), the Czech Science Foundation (15-09518S, 15-07268S, 17-07332S, and 17-31248A), and Institutional Research Concept (RVO: 61388971). This work was also supported by Charles University in Prague, Faculty of Medicine in Hradec Kralove, Czech Republic, project “PRVOUK” P37/10.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was reviewed and approved by the Institutional Review Committee (protocol no. PP77-2014), and all subjects participating in the study signed and dated Informed Consent and Fecal Donor Agreement forms.
- AARDA (2011) The cost burden of autoimmune disease: The latest front in the war on healthcare spending. http://www.diabetesed.net/page/_files/autoimmune-diseases.pdf. Accessed 16 Jan 2019
- Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K, Honda K (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341. https://doi.org/10.1126/science.1198469 CrossRefPubMedGoogle Scholar
- Bateman B, Warner JO, Hutchinson E, Dean T, Rowlandson P, Gant C, Grundy J, Fitzgerald C, Stevenson J (2004) The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children. Arch Dis Child 89:506–511. https://doi.org/10.1136/adc.2003.031435 CrossRefPubMedPubMedCentralGoogle Scholar
- Bloom SM, Bijanki VN, Nava GM, Sun L, Malvin NP, Donermeyer DL, Dunne WM Jr, Allen PM, Stappenbeck TS (2011) Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe 9:390–403. https://doi.org/10.1016/j.chom.2011.04.009 CrossRefPubMedPubMedCentralGoogle Scholar
- Boesten R, Schuren F, Ben Amor K (2011) Bifidobacterium population analysis in the infant gut by direct mapping of genomic hybridization patterns: potential for monitoring temporal development and effects of dietary regimens. Microb Biotechnol 4:417–427. https://doi.org/10.1111/j.1751-7915.2010.00216.x CrossRefPubMedPubMedCentralGoogle Scholar
- Ekmekciu I, Klitzing v E, Fiebiger U et al (2017) The probiotic compound VSL#3 modulates mucosal, peripheral, and systemic immunity following murine broad-spectrum antibiotic treatment. Front Cell Infect Microbiol 7:167. https://doi.org/10.3389/fcimb.2017.00167 CrossRefPubMedPubMedCentralGoogle Scholar
- Engelkirk PG, Duben-Engelkirk JL (2008) Laboratory diagnosis of infectious diseases. Lippincott Williams and Wilkins, BaltimoreGoogle Scholar
- Hickey CA, Kuhn KA, Donermeyer DL, Porter NT, Jin C, Cameron EA, Jung H, Kaiko GE, Wegorzewska M, Malvin NP, Glowacki RWP, Hansson GC, Allen PM, Martens EC, Stappenbeck TS (2015) Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles. Cell Host Microbe 17:672–680. https://doi.org/10.1016/j.chom.2015.04.002 CrossRefPubMedPubMedCentralGoogle Scholar
- Hrncir T, Stepankova R, Kozakova H, Hudcovic T, Tlaskalova-Hogenova H (2008) Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice. BMC Immunol 9:65. https://doi.org/10.1186/1471-2172-9-65 CrossRefPubMedPubMedCentralGoogle Scholar
- Hudcovic T, Kolinska J, Klepetar J, Stepankova R, Rezanka T, Srutkova D, Schwarzer M, Erban V, du Z, Wells JM, Hrncir T, Tlaskalova-Hogenova H, Kozakova H (2012) Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice. Clin Exp Immunol 167:356–365. https://doi.org/10.1111/j.1365-2249.2011.04498.x CrossRefPubMedPubMedCentralGoogle Scholar
- Kim SC, Tonkonogy SL, Albright CA, Tsang J, Balish EJ, Braun J, Huycke MM, Sartor RB (2005) Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 128:891–906. https://doi.org/10.1053/j.gastro.2005.02.009 CrossRefPubMedGoogle Scholar
- Malhotra B, Keshwani A, Kharkwal H (2015) Antimicrobial food packaging: potential and pitfalls. Front Microbiol 6. https://doi.org/10.3389/fmicb.2015.00611
- McCann D, Barrett A, Cooper A, Crumpler D, Dalen L, Grimshaw K, Kitchin E, Lok K, Porteous L, Prince E, Sonuga-Barke E, Warner JO, Stevenson J (2007) Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 370:1560–1567. https://doi.org/10.1016/S0140-6736(07)61306-3 CrossRefPubMedGoogle Scholar
- Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, Morita H, Hattori M, Yamamura T (2015) Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVA and IV clusters. PLoS One 10:e0137429. https://doi.org/10.1371/journal.pone.0137429 CrossRefPubMedPubMedCentralGoogle Scholar
- Mudie DM, Murray K, Hoad CL, Pritchard SE, Garnett MC, Amidon GL, Gowland PA, Spiller RC, Amidon GE, Marciani L (2014) Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state. Mol Pharm 11:3039–3047. https://doi.org/10.1021/mp500210c CrossRefPubMedGoogle Scholar
- Roca-Saavedra P, Mendez-Vilabrille V, Miranda JM, Nebot C, Cardelle-Cobas A, Franco CM, Cepeda A (2018) Food additives, contaminants and other minor components: effects on human gut microbiota-a review. J Physiol Biochem 74:69–83. https://doi.org/10.1007/s13105-017-0564-2 CrossRefPubMedGoogle Scholar
- Rosinger A, Herrick K, Gahche J, Park S (2017) Sugar-sweetened beverage consumption among U.S. youth, 2011–2014 NCHS data brief 1–8 https://www.cdc.gov/nchs/data/databriefs/db271.pdf. Accessed 10 June 2018
- Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, Marmon S, Neimann A, Brusca S, Patel T, Manasson J, Pamer EG, Littman DR, Abramson SB (2015) Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory. Arthritis Rheum 67:128–139. https://doi.org/10.1002/art.38892 CrossRefGoogle Scholar
- Shoenfeld Y, Cervera R, Gershwin ME (2010) Diagnostic criteria in autoimmune diseases. Humana Press, Totowa, NJGoogle Scholar
- Silbergeld EK, Graham J, Price LB (2008) Industrial food animal production, antimicrobial resistance, and human health. 29:151–169. https://doi.org/10.1146/annurev.publhealth.29.020907.090904
- Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Man Lei Y, Jabri B, Alegre ML, Chang EB, Gajewski TF (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science 350:1084–1089. https://doi.org/10.1126/science.aac4255 CrossRefPubMedPubMedCentralGoogle Scholar
- Steck N, Hoffmann M, Sava IG, Kim SC, Hahne H, Tonkonogy SL, Mair K, Krueger D, Pruteanu M, Shanahan F, Vogelmann R, Schemann M, Kuster B, Sartor RB, Haller D (2011) Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology 141:959–971. https://doi.org/10.1053/j.gastro.2011.05.035 CrossRefPubMedGoogle Scholar
- Sulavik MC, Houseweart C, Cramer C, Jiwani N, Murgolo N, Greene J, DiDomenico B, Shaw KJ, Miller GH, Hare R, Shimer G (2001) Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob Agents Chemother 45:1126–1136. https://doi.org/10.1128/AAC.45.4.1126-1136.2001 CrossRefPubMedPubMedCentralGoogle Scholar
- Technavio (2017) A New Report on the Global Food Additives Market from 2017–2021. https://www.businesswire.com/news/home/20171011005886/en/Food-Additives-Market%2D%2D-Drivers-Forecasts-Technavio. Accessed 10 June 2018
- Tlaskalova-Hogenova H, Stepankova R, Kozakova H et al (2011) The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol Immunol 8:110–120. https://doi.org/10.1038/cmi.2010.67 CrossRefPubMedPubMedCentralGoogle Scholar
- Willis AT (2014) Anaerobic bacteriology: clinical and laboratory practice. Butterworths, LondonGoogle Scholar
- Yuan J, Zhu L, Liu X, Li T, Zhang Y, Ying T, Wang B, Wang J, Dong H, Feng E, Li Q, Wang J, Wang H, Wei K, Zhang X, Huang C, Huang P, Huang L, Zeng M, Wang H (2006) A proteome reference map and proteomic analysis of Bifidobacterium longum NCC2705. Mol Cell Proteomics 5:1105–1118. https://doi.org/10.1074/mcp.M500410-MCP200 CrossRefPubMedGoogle Scholar