Abstract
A dense resident microbial community in the gut, referred as the commensal microbiota, coevolved with the host and is essential for many host physiological processes that include enhancement of the intestinal epithelial barrier, development of the immune system and acquisition of nutrients. A major function of the microbiota is protection against colonization by pathogens and overgrowth of indigenous pathobionts that can result from the disruption of the healthy microbial community. The mechanisms that regulate the ability of the microbiota to restrain pathogen growth are complex and include competitive metabolic interactions, localization to intestinal niches and induction of host immune responses. Pathogens, in turn, have evolved strategies to escape from commensal-mediated resistance to colonization. Thus, the interplay between commensals and pathogens or indigenous pathobionts is critical for controlling infection and disease. Understanding pathogen-commensal interactions may lead to new therapeutic approaches to treating infectious diseases.
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References
Hooper, L.V. & Macpherson, A.J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 10, 159–169 (2010).
Dridi, B., Raoult, D. & Drancourt, M. Archaea as emerging organisms in complex human microbiomes. Anaerobe 17, 56–63 (2011).
Pridmore, R.D. et al. The genome sequence of the probiotic intestinal bacterium Lactobacillus johnsonii NCC 533. Proc. Natl. Acad. Sci. USA 101, 2512–2517 (2004).
Turnbaugh, P.J., Backhed, F., Fulton, L. & Gordon, J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213–223 (2008).
Matamoros, S., Gras-Leguen, C., Le Vacon, F., Potel, G. & de La Cochetiere, M.F. Development of intestinal microbiota in infants and its impact on health. Trends Microbiol. 21, 167–173 (2013).
Hasegawa, M. et al. Transitions in oral and intestinal microflora composition and innate immune receptor-dependent stimulation during mouse development. Infect. Immun. 78, 639–650 (2010).
Koropatkin, N.M., Cameron, E.A. & Martens, E.C. How glycan metabolism shapes the human gut microbiota. Nat. Rev. Microbiol. 10, 323–335 (2012).
Willing, B. et al. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm. Bowel Dis. 15, 653–660 (2009).
Li, E. et al. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition. PLoS ONE 7, e26284 (2012).
Oh, P.L. et al. Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants. Am. J. Transplant. 12, 753–762 (2012).
Hammami, R., Fernandez, B., Lacroix, C. & Fliss, I. Anti-infective properties of bacteriocins: an update. Cell Mol. Life Sci. advance online publication, doi:10.1007/s00018-012-1202-3 (30 October 2012).
Schamberger, G.P. & Diez-Gonzalez, F. Selection of recently isolated colicinogenic Escherichia coli strains inhibitory to Escherichia coli O157:H7. J. Food Prot. 65, 1381–1387 (2002).
Turovskiy, Y., Sutyak Noll, K. & Chikindas, M.L. The aetiology of bacterial vaginosis. J. Appl. Microbiol. 110, 1105–1128 (2011).
Cherrington, C.A., Hinton, M., Pearson, G.R. & Chopra, I. Short-chain organic acids at ph 5.0 kill Escherichia coli and Salmonella spp. without causing membrane perturbation. J. Appl. Bacteriol. 70, 161–165 (1991).
Shin, R., Suzuki, M. & Morishita, Y. Influence of intestinal anaerobes and organic acids on the growth of enterohaemorrhagic Escherichia coli O157:H7. J. Med. Microbiol. 51, 201–206 (2002).
Fukuda, S. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011).
Ceuppens, S. et al. Enterotoxin production by Bacillus cereus under gastrointestinal conditions and their immunological detection by commercially available kits. Foodborne Pathog. Dis. 9, 1130–1136 (2012).
Momose, Y., Hirayama, K. & Itoh, K. Competition for proline between indigenous Escherichia coli and E. coli O157:H7 in gnotobiotic mice associated with infant intestinal microbiota and its contribution to the colonization resistance against E. coli O157:H7. Antonie van Leeuwenhoek 94, 165–171 (2008).
Momose, Y., Hirayama, K. & Itoh, K. Effect of organic acids on inhibition of Escherichia coli O157:H7 colonization in gnotobiotic mice associated with infant intestinal microbiota. Antonie van Leeuwenhoek 93, 141–149 (2008).
Fabich, A.J. et al. Comparison of carbon nutrition for pathogenic and commensal Escherichia coli strains in the mouse intestine. Infect. Immun. 76, 1143–1152 (2008).
Leatham, M.P. et al. Precolonized human commensal Escherichia coli strains serve as a barrier to E. coli O157:H7 growth in the streptomycin-treated mouse intestine. Infect. Immun. 77, 2876–2886 (2009).
Gantois, I. et al. Butyrate specifically down-regulates Salmonella pathogenicity island 1 gene expression. Appl. Environ. Microbiol. 72, 946–949 (2006).
Pacheco, A.R. et al. Fucose sensing regulates bacterial intestinal colonization. Nature 492, 113–117 (2012).
Marteyn, B. et al. Modulation of Shigella virulence in response to available oxygen in vivo. Nature 465, 355–358 (2010).
Kobayashi, K.S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731–734 (2005).
Vaishnava, S., Behrendt, C.L., Ismail, A.S., Eckmann, L. & Hooper, L.V. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc. Natl. Acad. Sci. USA 105, 20858–20863 (2008).
Vaishnava, S. et al. The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science 334, 255–258 (2011).
Satoh-Takayama, N. et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29, 958–970 (2008).
Sanos, S.L. et al. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat. Immunol. 10, 83–91 (2009).
Zheng, Y. et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14, 282–289 (2008).
Kiss, E.A. et al. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334, 1561–1565 (2011).
Qiu, J. et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36, 92–104 (2012).
Frantz, A.L. et al. Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides. Mucosal Immunol. 5, 501–512 (2012).
Fagarasan, S., Kawamoto, S., Kanagawa, O. & Suzuki, K. Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis. Annu. Rev. Immunol. 28, 243–273 (2010).
Suzuki, K. et al. The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut. Immunity 33, 71–83 (2010).
Strugnell, R.A. & Wijburg, O.L. The role of secretory antibodies in infection immunity. Nat. Rev. Microbiol. 8, 656–667 (2010).
Petnicki-Ocwieja, T. et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc. Natl. Acad. Sci. USA 106, 15813–15818 (2009).
Salzman, N.H. et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat. Immunol. 11, 76–83 (2010).
Macpherson, A.J., Geuking, M.B. & McCoy, K.D. Homeland security: IgA immunity at the frontiers of the body. Trends Immunol. 33, 160–167 (2012).
Franchi, L. et al. NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat. Immunol. 13, 449–456 (2012).
Ivanov, I.I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).
Bohnhoff, M., Drake, B.L. & Miller, C.P. Effect of streptomycin on susceptibility of intestinal tract to experimental Salmonella infection. Proc. Soc. Exp. Biol. Med. 86, 132–137 (1954).
Endt, K. et al. The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea. PLoS Pathog. 6, e1001097 (2010).
Ayres, J.S., Trinidad, N.J. & Vance, R.E. Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota. Nat. Med. 18, 799–806 (2012).
Rupnik, M., Wilcox, M.H. & Gerding, D.N. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat. Rev. Microbiol. 7, 526–536 (2009).
Ng, J. et al. Clostridium difficile toxin-induced inflammation and intestinal injury are mediated by the inflammasome. Gastroenterology 139, 542–552 (2010).
Hasegawa, M. et al. Protective role of commensals against Clostridium difficile infection via an IL-1beta-mediated positive-feedback loop. J. Immunol. 189, 3085–3091 (2012).
Arias, C.A. & Murray, B.E. The rise of the Enterococcus: beyond vancomycin resistance. Nat. Rev. Microbiol. 10, 266–278 (2012).
Brandl, K. et al. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 455, 804–807 (2008).
Kinnebrew, M.A. et al. Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection. J. Infect. Dis. 201, 534–543 (2010).
Ubeda, C. et al. Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization. Infect. Immun. 81, 965–973 (2013).
Giel, J.L., Sorg, J.A., Sonenshein, A.L. & Zhu, J. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLoS ONE 5, e8740 (2010).
Kane, M. et al. Successful transmission of a retrovirus depends on the commensal microbiota. Science 334, 245–249 (2011).
Kuss, S.K. et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 334, 249–252 (2011).
Le Bouguenec, C. & Schouler, C. Sugar metabolism, an additional virulence factor in enterobacteria. Int. J. Med. Microbiol. 301, 1–6 (2011).
Perna, N.T. et al. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409, 529–533 (2001).
Bertin, Y. et al. Enterohaemorrhagic Escherichia coli gains a competitive advantage by using ethanolamine as a nitrogen source in the bovine intestinal content. Environ. Microbiol. 13, 365–377 (2011).
Kamada, N. et al. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336, 1325–1329 (2012).
Crosa, J.H. & Walsh, C.T. Genetics and assembly line enzymology of siderophore biosynthesis in bacteria. Microbiol. Mol. Biol. Rev. 66, 223–249 (2002).
Fischbach, M.A., Lin, H., Liu, D.R. & Walsh, C.T. How pathogenic bacteria evade mammalian sabotage in the battle for iron. Nat. Chem. Biol. 2, 132–138 (2006).
Lupp, C. et al. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2, 204 (2007).
Furne, J., Springfield, J., Koenig, T., DeMaster, E. & Levitt, M.D. Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa. Biochem. Pharmacol. 62, 255–259 (2001).
Levitt, M.D., Furne, J., Springfield, J., Suarez, F. & DeMaster, E. Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa. J. Clin. Invest. 104, 1107–1114 (1999).
Winter, S.E. et al. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature 467, 426–429 (2010).
Thiennimitr, P. et al. Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota. Proc. Natl. Acad. Sci. USA 108, 17480–17485 (2011).
Kolios, G., Valatas, V. & Ward, S.G. Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzle. Immunology 113, 427–437 (2004).
Reinders, C.A. et al. Rectal nitric oxide and fecal calprotectin in inflammatory bowel disease. Scand. J. Gastroenterol. 42, 1151–1157 (2007).
Winter, S.E. et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339, 708–711 (2013).
Wu, L. et al. Recognition of host immune activation by Pseudomonas aeruginosa. Science 309, 774–777 (2005).
Kaper, J.B., Nataro, J.P. & Mobley, H.L. Pathogenic Escherichia coli. Nat. Rev. Microbiol. 2, 123–140 (2004).
Reeves, A.E., Koenigsknecht, M.J., Bergin, I.L. & Young, V.B. Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae. Infect. Immun. 80, 3786–3794 (2012).
van Nood, E. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407–415 (2013).
Petrof, E.O. et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut. Microbiome 1, 3 (2013).
Ubeda, C. et al. Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice. J. Exp. Med. 209, 1445–1456 (2012).
Acknowledgements
We thank E. Martens for critical review of the manuscript. Studies on the microbiota in our laboratory are supported by grants from US National Institutes of Health, and the Bill & Melinda Gates Foundation. N.K. is supported by a Research Fellowship from the Crohn's and Colitis Foundation of America.
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Kamada, N., Chen, G., Inohara, N. et al. Control of pathogens and pathobionts by the gut microbiota. Nat Immunol 14, 685–690 (2013). https://doi.org/10.1038/ni.2608
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DOI: https://doi.org/10.1038/ni.2608
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