Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

An insider's perspective: Bacteroides as a window into the microbiome

Abstract

Over the last decade, our appreciation for the contribution of resident gut microorganisms—the gut microbiota—to human health has surged. However, progress is limited by the sheer diversity and complexity of these microbial communities. Compounding the challenge, the majority of our commensal microorganisms are not close relatives of Escherichia coli or other model organisms and have eluded culturing and manipulation in the laboratory. In this Review, we discuss how over a century of study of the readily cultured, genetically tractable human gut Bacteroides has revealed important insights into the biochemistry, genomics and ecology that make a gut bacterium a gut bacterium. While genome and metagenome sequences are being produced at breakneck speed, the Bacteroides provide a significant ‘jump-start’ on uncovering the guiding principles that govern microbiota–host and inter-bacterial associations in the gut that will probably extend to many other members of this ecosystem.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Global distributions and abundances of human gut microorganisms at the phylum and genus levels.
Figure 2: Consumption and production of polysaccharides in Bacteroides.
Figure 3: Commensal colonization of colonic crypts.
Figure 4: Mechanisms of inter-bacterial cooperation and antagonism among Bacteroides.

Similar content being viewed by others

References

  1. Sender, R., Fuchs, S. & Milo, R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164, 337–340 (2016).

    Article  CAS  PubMed  Google Scholar 

  2. Savage, D. C. Microbial ecology of the gastrointestinal tract. Annu. Rev. Microbiol. 31, 107–133 (1977).

    Article  CAS  PubMed  Google Scholar 

  3. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lozupone, C. A., Stombaugh, J. I., Gordon, J. I. & Jansson, J. K. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bäckhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A. & Gordon, J. I. Host-bacterial mutualism in the human intestine. Science 307, 1915–1920 (2005).

    Article  PubMed  CAS  Google Scholar 

  6. Koenig, J. E. et al. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl Acad. Sci. USA 108, 4578–4585 (2011).

    Article  CAS  PubMed  Google Scholar 

  7. Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A. & Brown, P. O. Development of the human infant intestinal microbiota. PLoS Biol. 5, e177 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Faith, J. J. et al. The long-term stability of the human gut microbiota. Science 341, 1237439 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

  11. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

    Article  CAS  PubMed  Google Scholar 

  12. Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Browne, H. P. et al. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature 533, 543–546 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rettedal, E. A., Gumpert, H. & Sommer, M. O. Cultivation-based multiplex phenotyping of human gut microbiota allows targeted recovery of previously uncultured bacteria. Nat. Commun. 5, 4714 (2014).

    Article  CAS  PubMed  Google Scholar 

  15. Sommer, M. O. Advancing gut microbiome research using cultivation. Curr. Opin. Microbiol. 27, 127–132 (2015).

    Article  CAS  PubMed  Google Scholar 

  16. Goodman, A. L. et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc. Natl Acad. Sci. USA 108, 6252–6257 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lagier, J.-C. C. et al. Culture of previously uncultured members of the human gut microbiota by culturomics. Nat. Microbiol. 1, 16203 (2016).

    Article  CAS  PubMed  Google Scholar 

  18. Distaso, A. Contribution à l’étude sur l’intoxication intestinale. Centralb. f. Bakteriol. 62, 433 (1912).

    Google Scholar 

  19. Eggerth, A. H. & Gagnon, B. H. The Bacteroides of human feces. J. Bacteriol. 25 389–413 (1933).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Veillon, M. H. & Zuber, H. Recherches sur quelques microbes strictement anaérobies et leur rôle en pathologie. Arch. Med. Exp. Anat. Pathol. 10, 517–545 (1898).

    Google Scholar 

  21. Ley, R. E. et al. Evolution of mammals and their gut microbes. Science 320, 1647–1651 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ley, R. E., Lozupone, C. A., Hamady, M., Knight, R. & Gordon, J. I. Worlds within worlds: evolution of the vertebrate gut microbiota. Nat. Rev. Microbiol. 6, 776–788 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kraus, D. Concepts of Modern Biology (Globe Book Company, 1993).

    Google Scholar 

  24. Helander, H. F. & Fändriks, L. Surface area of the digestive tract – revisited. Scand. J. Gastroenterol. 49, 681–689 (2014).

    Article  PubMed  Google Scholar 

  25. Donaldson, G. P., Lee, S. M. & Mazmanian, S. K. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 14, 20–32 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Evans, D. F., Pye, G., Bramley, R., Clark, A. G. & Dyson, T. J. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 29, 1035–1041 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Albenberg, L., Esipova, T. V., Judge, C. P. & Bittinger, K. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota. Gastroenterology 147, 1055–1063 (2014).

    Article  PubMed  Google Scholar 

  28. Stecher, B., Maier, L. & Hardt, W.-D. D. ‘Blooming’ in the gut: how dysbiosis might contribute to pathogen evolution. Nat. Rev. Microbiol. 11, 277–284 (2013).

    Article  CAS  PubMed  Google Scholar 

  29. Belkaid, Y. & Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 157, 121–141 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kurokawa, K., Itoh, T., Kuwahara, T. & Oshima, K. Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res. 14, 169–181 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Baughn, A. D. & Malamy, M. H. The strict anaerobe Bacteroides fragilis grows in and benefits from nanomolar concentrations of oxygen. Nature 427, 441–444 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Meehan, B. M., Baughn, A. D., Gallegos, R. & Malamy, M. H. Inactivation of a single gene enables microaerobic growth of the obligate anaerobe Bacteroides fragilis. Proc. Natl Acad. Sci. USA 109, 12153–12158 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Rocha, E. R. & Smith, C. J. Ferritin-like family proteins in the anaerobe Bacteroides fragilis: when an oxygen storm is coming, take your iron to the shelter. Biometals 26, 577–591 (2013).

    Article  CAS  PubMed  Google Scholar 

  34. Smalley, D., Rocha, E. R. & Smith, C. J. Aerobic-type ribonucleotide reductase in the anaerobe Bacteroides fragilis. J. Bacteriol. 184, 895–903 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rocha, E. R., Selby, T., Coleman, J. P. & Smith, J. C. Oxidative stress response in an anaerobe, Bacteroides fragilis: a role for catalase in protection against hydrogen peroxide. J. Bacteriol. 178, 6895–6903 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bry, L., Falk, P. G., Midtvedt, T. & Gordon, J. I. A model of host–microbial interactions in an open mammalian ecosystem. Science 273, 1380–1383 (1996).

    Article  CAS  PubMed  Google Scholar 

  37. Ng, K. M. et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502, 96–99 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wright, E. M., Martín, M. G. & Turk, E. Intestinal absorption in health and disease—sugars. Best. Pract. Res. Clin. Gastroenterol. 17, 943–956 (2003).

    Article  CAS  PubMed  Google Scholar 

  39. Salyers, A. A., Vercellotti, J. R. & West, S. E. Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon. Appl. Environ. Microbiol. 33, 319–322 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. McNeil, N. I. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 39, 338–342 (1984).

    Article  CAS  PubMed  Google Scholar 

  41. Lee, S. M. et al. Bacterial colonization factors control specificity and stability of the gut microbiota. Nature 501, 426–429 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Anderson, K. L. & Salyers, A. A. Biochemical evidence that starch breakdown by Bacteroides thetaiotaomicron involves outer membrane starch-binding sites and periplasmic starch-degrading enzymes. J. Bacteriol. 171, 3192–3198 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Anderson, K. L. & Salyers, A. A. Genetic evidence that outer membrane binding of starch is required for starch utilization by Bacteroides thetaiotaomicron. J. Bacteriol. 171, 3199–3204 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Martens, E. C., Chiang, H. C. & Gordon, J. I. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 4, 447–457 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Koropatkin, N. M., Cameron, E. A. & Martens, E. C. How glycan metabolism shapes the human gut microbiota. Nat. Rev. Microbiol. 10, 323–335 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Motherway, M. et al. Characterization of ApuB, an extracellular type II amylopullulanase from Bifidobacterium breve UCC2003. Appl. Environ. Microbiol. 74, 6271–6279 (2008).

    Article  CAS  Google Scholar 

  47. Xu, J. et al. A genomic view of the human–Bacteroides thetaiotaomicron symbiosis. Science 299, 2074–2076 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Xu, J. et al. Evolution of symbiotic bacteria in the distal human intestine. PLoS Biol. 5, e156 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Cameron, E. A. et al. Multifunctional nutrient-binding proteins adapt human symbiotic bacteria for glycan competition in the gut by separately promoting enhanced sensing and catalysis. mBio 5, e01441–14 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Martens, E. C., Roth, R., Heuser, J. E. & Gordon, J. I. Coordinate regulation of glycan degradation and polysaccharide capsule biosynthesis by a prominent human gut symbiont. J. Biol. Chem. 284, 18445–18457 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lynch, J. B. & Sonnenburg, J. L. Prioritization of a plant polysaccharide over a mucus carbohydrate is enforced by a Bacteroides hybrid two-component system. Mol. Microbiol. 85, 478–491 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sonnenburg, E. D. et al. A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism. Proc. Natl Acad. Sci. USA 103, 8834–8839 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Townsend, G. E., Raghavan, V., Zwir, I. & Groisman, E. A. Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems. Proc. Natl Acad. Sci. USA 110, 161–169 (2013).

    Article  Google Scholar 

  54. Raghavan, V., Lowe, E. C., Townsend, G. E., Bolam, D. N. & Groisman, E. A. Tuning transcription of nutrient utilization genes to catabolic rate promotes growth in a gut bacterium. Mol. Microbiol. 93, 1010–1025 (2014).

    Article  CAS  PubMed  Google Scholar 

  55. Schwalm, N. D., Townsend, G. E. & Groisman, E. A. Multiple signals govern utilization of a polysaccharide in the gut bacterium Bacteroides thetaiotaomicron. mBio 7, e01342–16 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cann, I., Bernardi, R. C. & Mackie, R. I. Cellulose degradation in the human gut: Ruminococcus champanellensis expands the cellulosome paradigm. Environ. Microbiol. 18, 307–310 (2016).

    Article  PubMed  Google Scholar 

  57. Artzi, L., Bayer, E. A. & Moraïs, S. Cellulosomes: bacterial nanomachines for dismantling plant polysaccharides. Nat. Rev. Microbiol. 15, 83–95 (2016).

    Article  PubMed  CAS  Google Scholar 

  58. Sonnenburg, J. L. et al. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science 307, 1955–1959 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Sonnenburg, E. D. et al. Diet-induced extinctions in the gut microbiota compound over generations. Nature 529, 212–215 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Pumbwe, L., Skilbeck, C. A. & Wexler, H. M. The Bacteroides fragilis cell envelope: quarterback, linebacker, coach-or all three? Anaerobe 12, 211–220 (2006).

    Article  CAS  PubMed  Google Scholar 

  61. Wangdi, T., Lee, C. Y., Spees, A. M., Yu, C. & Kingsbury, D. D. The Vi capsular polysaccharide enables Salmonella enterica serovar typhi to evade microbe-guided neutrophil chemotaxis. PLoS Pathog. 10, e1004306 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Doorduijn, D. J., Rooijakkers, S. H., van Schaik, W. & Bardoel, B. W. Complement resistance mechanisms of Klebsiella pneumoniae. Immunobiology 221, 1102–1109 (2016).

    Article  CAS  PubMed  Google Scholar 

  63. Krinos, C. M. et al. Extensive surface diversity of a commensal microorganism by multiple DNA inversions. Nature 414, 555–558 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Chatzidaki-Livanis, M., Weinacht, K. G. & Comstock, L. E. Trans locus inhibitors limit concomitant polysaccharide synthesis in the human gut symbiont Bacteroides fragilis. Proc. Natl Acad. Sci. USA 107, 11976–11980 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Comstock, L. E. & Kasper, D. L. Bacterial glycans: key mediators of diverse host immune responses. Cell 126, 847–850 (2006).

    Article  CAS  PubMed  Google Scholar 

  66. Coyne, M. J. & Comstock, L. E. Niche-specific features of the intestinal Bacteroidales. J. Bacteriol. 190, 736–742 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Fletcher, C. M., Coyne, M. J., Bentley, D. L., Villa, O. F. & Comstock, L. E. Phase-variable expression of a family of glycoproteins imparts a dynamic surface to a symbiont in its human intestinal ecosystem. Proc. Natl Acad. Sci. USA 104, 2413–2418 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Coyne, M. J., Chatzidaki-Livanis, M., Paoletti, L. C. & Comstock, L. E. Role of glycan synthesis in colonization of the mammalian gut by the bacterial symbiont Bacteroides fragilis. Proc. Natl Acad. Sci. USA 105, 13099–13104 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Peterson, D. A., McNulty, N. P., Guruge, J. L. & Gordon, J. I. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe 2, 328–339 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Shen, Y. et al. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12, 509–520 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chu, H. et al. Gene–microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science 352, 1116–1120 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

    Article  PubMed  Google Scholar 

  74. Fischbach, M. A. & Sonnenburg, J. L. Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe 10, 336–347 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Sonnenburg, E. D. & Sonnenburg, J. L. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metab. 20, 779–786 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Harmsen, H. J. et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J. Pediatr. Gastroenterol. Nutr. 30, 61–67 (2000).

    Article  CAS  PubMed  Google Scholar 

  77. Marcobal, A. et al. Consumption of human milk oligosaccharides by gut-related microbes. J. Agric. Food. Chem. 58, 5334–5340 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Marcobal, A. et al. Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. Cell Host Microbe 10, 507–514 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kunz, C., Rudloff, S., Baier, W., Klein, N. & Strobel, S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu. Rev. Nutr. 20, 699–722 (2000).

    Article  CAS  PubMed  Google Scholar 

  80. Ninonuevo, M. R., Park, Y., Yin, H. & Zhang, J. A strategy for annotating the human milk glycome. J. Agric. Food Chem. 54 7471–7480 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Charbonneau, M. R. et al. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell 164, 859–871 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Fukuda, S. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011).

    Article  CAS  PubMed  Google Scholar 

  83. Saez-Lara, M. J. & Gomez-Llorente, C. The role of probiotic lactic acid bacteria and bifidobacteria in the prevention and treatment of inflammatory bowel disease and other related diseases: a systematic review of randomized human clinical trials. Biomed. Res. Int. 2015, 505878 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Mahowald, M. A. et al. Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla. Proc. Natl Acad. Sci. USA 106, 5859–5864 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Sonnenburg, J. L., Chen, C. T. L. & Gordon, J. I. Genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host. PLoS Biol. 4, e413 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Allen, R. H. & Stabler, S. P. Identification and quantitation of cobalamin and cobalamin analogues in human feces. Am. J. Clin. Nutr. 87, 1324–1335 (2008).

    Article  CAS  PubMed  Google Scholar 

  87. Degnan, P. H., Taga, M. E. & Goodman, A. L. Vitamin B12 as a modulator of gut microbial ecology. Cell Metab. 20, 769–778 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Degnan, P. H., Barry, N. A., Mok, K. C., Taga, M. E. & Goodman, A. L. Human gut microbes use multiple transporters to distinguish vitamin B12 analogs and compete in the gut. Cell Host Microbe 15, 47–57 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Goodman, A. L. et al. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6, 279–289 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Rakoff-Nahoum, S., Coyne, M. J. & Comstock, L. E. An ecological network of polysaccharide utilization among human intestinal symbionts. Curr. Biol. 24, 40–49 (2014).

    Article  CAS  PubMed  Google Scholar 

  91. Rakoff-Nahoum, S., Foster, K. R. & Comstock, L. E. The evolution of cooperation within the gut microbiota. Nature 533, 255–259 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Elhenawy, W., Debelyy, M. O. & Feldman, M. F. Preferential packing of acidic glycosidases and proteases into Bacteroides outer membrane vesicles. mBio 5, e00909–14 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Kulp, A. & Kuehn, M. J. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu. Rev. Microbiol. 64, 163 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. & Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005).

    Article  CAS  PubMed  Google Scholar 

  95. Cotter, P. D., Hill, C. & Ross, R. P. Bacteriocins: developing innate immunity for food. Nat. Rev. Microbiol. 3, 777–788 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. Kommineni, S. et al. Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract. Nature 526, 719–722 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chatzidaki-Livanis, M., Coyne, M. J. & Comstock, L. E. An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins. Mol. Microbiol. 94, 1361–1374 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Roelofs, K. G., Coyne, M. J., Gentyala, R. R., Chatzidaki-Livanis, M. & Comstock, L. E. Bacteroidales secreted antimicrobial proteins target surface molecules necessary for gut colonization and mediate competition in vivo. mBio 7, e01055–16 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Tomita, H., Fujimoto, S., Tanimoto, K. & Ike, Y. Cloning and genetic and sequence analyses of the bacteriocin 21 determinant encoded on the Enterococcus faecalis pheromone-responsive conjugative plasmid pPD1. J. Bacteriol. 179, 7843–7855 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Russell, A. B. et al. A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism. Cell Host Microbe 16, 227–236 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Coyne, M. J., Zitomersky, N. L., McGuire, A. M., Earl, A. M. & Comstock, L. E. Evidence of extensive DNA transfer between Bacteroidales species within the human gut. mBio 5, 14 (2014).

    Article  CAS  Google Scholar 

  102. Russell, A. B., Peterson, S. B. & Mougous, J. D. Type VI secretion system effectors: poisons with a purpose. Nat. Rev. Microbiol. 12, 137–148 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Coyne, M. J., Roelofs, K. G. & Comstock, L. E. Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements. BMC Genomics 17, 58 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Wexler, A. G. et al. Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proc. Natl Acad. Sci. USA 113, 3639–3644 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Chatzidaki-Livanis, M., Geva-Zatorsky, N. & Comstock, L. E. Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species. Proc. Natl Acad. Sci. USA 113, 3627–3632 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Whitney, J. C. et al. An interbacterial NAD(P)+ glycohydrolase toxin requires elongation factor Tu for delivery to target cells. Cell 163, 607–619 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Hecht, A. L. et al. Strain competition restricts colonization of an enteric pathogen and prevents colitis. EMBO Rep. 17, 1281–1291 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Moreau, M. C., Ducluzeau, R. & Guy-Grand, D. Increase in the population of duodenal immunoglobulin A plasmocytes in axenic mice associated with different living or dead bacterial strains of intestinal origin. Infect. Immun. 21, 532–539 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Macpherson, A. J. & Harris, N. L. Opinion: interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 4, 478–485 (2004).

    Article  CAS  PubMed  Google Scholar 

  110. Sprinz, H. et al. The response of the germfree guinea pig to oral bacterial challenge with Escherichia coli and Shigella flexneri. Am. J. Pathol. 39, 681–695 (1961).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Ivanov, I. I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337–349 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Round, J. L. & Mazmanian, S. K. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl Acad. Sci. USA 107, 12204–12209 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Neff, C. P. et al. Diverse intestinal bacteria contain putative zwitterionic capsular polysaccharides with anti-inflammatory properties. Cell Host Microbe 20, 535–547 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Vatanen, T. et al. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165, 842–853 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Atarashi, K. et al. Induction of colonic regulatory T Cells by indigenous Clostridium species. Science 331, 337–341 (2011).

    Article  CAS  PubMed  Google Scholar 

  117. Rosenshine, I., Ruschkowski, S. & Stein, M. A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation. EMBO J. 15, 2613–2624 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Kaper, J. B., Nataro, J. P. & Mobley, H. L. T. Pathogenic Escherichia coli. Nat. Rev. Microbiol. 2, 123–140 (2004).

    CAS  Google Scholar 

  119. Curtis, M. M. et al. The gut commensal Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape. Cell Host Microbe 16, 759–769 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Pacheco, A. R. et al. Fucose sensing regulates bacterial intestinal colonization. Nature 492, 113–117 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Huang, Y.-L. L., Chassard, C., Hausmann, M., von Itzstein, M. & Hennet, T. Sialic acid catabolism drives intestinal inflammation and microbial dysbiosis in mice. Nat. Commun. 6, 8141 (2015).

    Article  CAS  PubMed  Google Scholar 

  122. Rivera-Chávez, F. et al. Depletion of butyrate-producing Clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella. Cell Host Microbe 19, 443–454 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. McClean, K. L., Sheehan, G. J. & Harding, G. K. Intraabdominal infection: a review. Clin. Infect. Dis. 19, 100–116 (1994).

    Article  CAS  PubMed  Google Scholar 

  124. Brook, I. & Frazier, E. H. Aerobic and anaerobic microbiology in intra-abdominal infections associated with diverticulitis. J. Med. Microbiol. 49, 827–830 (2000).

    Article  CAS  PubMed  Google Scholar 

  125. Vaishnava, S. et al. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334, 255–258 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Runeberg, B. Studien über die bei peritonealen infektionem appendikularen ursprungs vorkommenden sauerstofftoleranten, mit besonderer berücksichtigung ihrer bedeutung für die pathogenese derartiger peritonitiden. Arb. a. d. Path. Inst. d. Univ. Helsinfors 1, 271 (1908).

    Google Scholar 

  127. Heyde, M. Bakteriologische und experimentalle untersuchungen zur aetiologie der wurmfortsatzentzündung (mit besondere berücksichtigung der anaeroben bakterien). Beitr. z. klin. Chir. 76, 1 (1911).

    Google Scholar 

  128. Castellani, A. & Chalmers, A. J. Manual of Tropical Medicine (Bailliere, Tindall & Cox, 1919).

    Book  Google Scholar 

  129. Shah, H. N. The Genus Bacteroides and Related Taxa (Springer, 1992).

    Book  Google Scholar 

  130. Polk, B. F. & Kasper, D. L. Bacteroides fragilis subspecies in clinical isolates. Annu. Int. Med. 86, 569–571 (1977).

    Article  CAS  Google Scholar 

  131. Dürr, U. H. N., Sudheendra, U. S. & Ramamoorthy, A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim. Biophys. Acta 1758, 1408–1425 (2006).

    Article  PubMed  CAS  Google Scholar 

  132. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389–395 (2002).

    Article  CAS  PubMed  Google Scholar 

  133. Cullen, T. W. et al. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation. Science 347, 170–175 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Faith, J. J., McNulty, N. P., Rey, F. E. & Gordon, J. I. Predicting a human gut microbiota's response to diet in gnotobiotic mice. Science 333, 101–104 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. McNulty, N. P. et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci. Transl. Med. 3, 106ra106 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Arrieta, M.-C. C., Walter, J. & Finlay, B. B. Human microbiota-associated mice: a model with challenges. Cell Host Microbe 19, 575–578 (2016).

    Article  CAS  PubMed  Google Scholar 

  137. Baxter, N. T., Zackular, J. P., Chen, G. Y. & Schloss, P. D. Structure of the gut microbiome following colonization with human feces determines colonic tumor burden. Microbiome 2, 20 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Lagier, J.-C. C. et al. The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota. Clin. Microbiol. Rev. 28, 237–264 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Palm, N. W. et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158, 1000–1010 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Salyers, A. A., Bonheyo, G. & Shoemaker, N. B. Starting a new genetic system: lessons from Bacteroides. Methods 20, 35–46 (2000).

    Article  CAS  PubMed  Google Scholar 

  141. Wu, M. et al. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides. Science 350, aac5992 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Mimee, M., Tucker, A. C., Voigt, C. A. & Lu, T. K. Programming a human commensal bacterium, Bacteroides thetaiotaomicron, to sense and respond to stimuli in the murine gut microbiota. Cell Syst. 1, 62–71 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Kotula, J. W. et al. Programmable bacteria detect and record an environmental signal in the mammalian gut. Proc. Natl Acad. Sci. USA 111, 4838–4843 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Biteen, J. S. et al. Tools for the Microbiome: Nano and Beyond (ACS Nano, 2015).

    Google Scholar 

  145. Earle, K. A. et al. Quantitative imaging of gut microbiota spatial organization. Cell Host Microbe 18, 478–488 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Geva-Zatorsky, N. et al. In vivo imaging and tracking of host–microbiota interactions via metabolic labeling of gut anaerobic bacteria. Nat. Med. 21, 1091–1100 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Nishijima, S. et al. The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Res. 23, 125–133 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank W. Schofield and B. Lim for careful reading of the manuscript. Support for this work was provided by the National Institutes of Health (GM105456 and GM118159), the Pew Scholars Program, and the Burroughs Wellcome Fund to A.L.G. A.G.W. is supported by a fellowship from the Gruber Foundation.

Author information

Authors and Affiliations

Authors

Contributions

A.G.W. drafted the manuscript and prepared figures. A.G.W. and A.L.G. edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Andrew L. Goodman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wexler, A., Goodman, A. An insider's perspective: Bacteroides as a window into the microbiome. Nat Microbiol 2, 17026 (2017). https://doi.org/10.1038/nmicrobiol.2017.26

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/nmicrobiol.2017.26

This article is cited by

Search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology