1 Sender, R., Fuchs, S. & Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 14, e1002533 (2016).

2 Human Microbiome Project, C. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012). This study represents a comprehensive characterization of the human microbiota in health for multiple body sites.

3 Donaldson, G. P., Lee, S. M. & Mazmanian, S. K. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 14, 20–32 (2016).

4 Johansson, M. E. et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl Acad. Sci. 105, 15064–15069 (2008).

5 Ley, R. E. et al. Evolution of mammals and their gut microbes. Science 320, 1647–1651 (2008). This study sequenced the gut microbiota of humans and 59 other mammalian species and showed that herbivores have more diverse microbiota than carnivores.

6 Lehrer, R. I. & Lu, W. α-Defensins in human innate immunity. Immunol. Rev. 245, 84–112 (2012).

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

8 Suzuki, K. et al. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc. Natl Acad. Sci. USA 101, 1981–1986 (2004).

9 Liu, S. et al. The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe 19, 32–43 (2016).

10 Levin, B. J. et al. A prominent glycyl radical enzyme in human gut microbiomes metabolizes trans-4-hydroxy-l-proline. Science 355, eaai8386 (2017).

11 Ochman, H. et al. Evolutionary relationships of wild hominids recapitulated by gut microbial communities. PLoS Biol. 8, e1000546 (2010).

12 Moeller, A. H. et al. Cospeciation of gut microbiota with hominids. Science 353, 380–382 (2016).

13 Seedorf, H. et al. Bacteria from diverse habitats colonize and compete in the mouse gut. Cell 159, 253–266 (2014).

14 Goodrich, J. K. et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19, 731–743 (2016).

15 Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014).

16 Xie, H. et al. Shotgun metagenomics of 250 adult twins reveals genetic and environmental impacts on the gut microbiome. Cell Syst. 3, 572–584e573 (2016).

17 Thaiss, C. A. et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 159, 514–529 (2014).

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

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

20 Knights, D. et al. Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med. 6, 107 (2014). This GWAS of 474 individuals found that Enterobacteriaceae are significantly enriched in IBD.

21 Spor, A., Koren, O. & Ley, R. Unravelling the effects of the environment and host genotype on the gut microbiome. Nat. Rev. Microbiol. 9, 279–290 (2011).

22 Wang, J. et al. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat. Genet. 48, 1396–1406 (2016).

23 Turpin, W. et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat. Genet. 48, 1413–1417 (2016).

24 Bonder, M. J. et al. The effect of host genetics on the gut microbiome. Nat. Genet. 48, 1407–1412 (2016).

25 Blekhman, R. et al. Host genetic variation impacts microbiome composition across human body sites. Genome Biol. 16, 191 (2015).

26 Davenport, E. R. et al. Genome-wide association studies of the human gut microbiota. PLoS ONE 10, e0140301 (2015).

27 Sayin, S. I. et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17, 225–235 (2013).

28 Sentausa, E. & Fournier, P. E. Advantages and limitations of genomics in prokaryotic taxonomy. Clin. Microbiol. Infect. 19, 790–795 (2013).

29 Xavier, R. J. & Podolsky, D. K. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427–434 (2007).

30 Khor, B., Gardet, A. & Xavier, R. J. Genetics and pathogenesis of inflammatory bowel disease. Nature 474, 307–317 (2011).

31 Hugot, J. P. et al. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature 379, 821–823 (1996).

32 Hugot, J. P. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599–603 (2001).

33 Ogura, Y. et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603–606 (2001).

34 Cavanaugh, J. et al. International collaboration provides convincing linkage replication in complex disease through analysis of a large pooled data set: Crohn disease and chromosome 16. Am. J. Hum. Genet. 68, 1165–1171 (2001).

35 Hampe, J. et al. Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet 357, 1925–1928 (2001).

36 Philpott, D. J., Sorbara, M. T., Robertson, S. J., Croitoru, K. & Girardin, S. E. NOD proteins: regulators of inflammation in health and disease. Nat. Rev. Immunol. 14, 9–23 (2014).

37 Inohara, N. et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J. Biol. Chem. 278, 5509–5512 (2003).

38 Girardin, S. E. et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J. Biol. Chem. 278, 8869–8872 (2003).

39 Eckmann, L. & Karin, M. NOD2 and Crohn's disease: loss or gain of function? Immunity 22, 661–667 (2005).

40 Fritz, J. H. et al. Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists. Eur. J. Immunol. 35, 2459–2470 (2005).

41 Cho, J. H. & Abraham, C. Inflammatory bowel disease genetics: Nod2. Annu. Rev. Med. 58, 401–416 (2007).

42 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).

43 Couturier-Maillard, A. et al. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J. Clin. Invest. 123, 700–711 (2013).

44 Wlodarska, M., Kostic, A. D. & Xavier, R. J. An integrative view of microbiome-host interactions in inflammatory bowel diseases. Cell Host Microbe 17, 577–591 (2015).

45 Wehkamp, J. et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal α-defensin expression. Gut 53, 1658–1664 (2004).

46 Kobayashi, K. S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731–734 (2005).

47 Knights, D., Lassen, K. G. & Xavier, R. J. Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome. Gut 62, 1505–1510 (2013).

48 Chassaing, B. et al. Crohn disease—associated adherent-invasive E. coli bacteria target mouse and human Peyer's patches via long polar fimbriae. J. Clin. Invest. 121, 966–975 (2011).

49 Lapaquette, P., Bringer, M. A. & Darfeuille-Michaud, A. Defects in autophagy favour adherent-invasive Escherichia coli persistence within macrophages leading to increased pro-inflammatory response. Cell. Microbiol. 14, 791–807 (2012).

50 Li, D. et al. A pleiotropic missense variant in SLC39A8 is associated with Crohn's disease and human gut microbiome composition. Gastroenterology 151, 724–732 (2016).

51 Iliev, I. D. et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336, 1314–1317 (2012).

52 Sokol, H. et al. Card9 mediates intestinal epithelial cell restitution, T-helper 17 responses, and control of bacterial infection in mice. Gastroenterology 145, 591–601e593 (2013).

53 Lamas, B. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat. Med. 22, 598–605 (2016).

54 Lewis, J. D. et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn's disease. Cell Host Microbe 18, 489–500 (2015).

55 Boltin, D., Perets, T. T., Vilkin, A. & Niv, Y. Mucin function in inflammatory bowel disease: an update. J. Clin. Gastroenterol. 47, 106–111 (2013).

56 Smith, A. C. & Podolsky, D. K. Colonic mucin glycoproteins in health and disease. Clin. Gastroenterol. 15, 815–837 (1986).

57 Li, H. et al. The outer mucus layer hosts a distinct intestinal microbial niche. Nat. Commun. 6, 8292 (2015).

58 Macfarlane, G. T., Gibson, G. R. & Cummings, J. H. Comparison of fermentation reactions in different regions of the human colon. J. Appl. Bacteriol. 72, 57–64 (1992).

59 Macfarlane, S., Woodmansey, E. J. & Macfarlane, G. T. Colonization of mucin by human intestinal bacteria and establishment of biofilm communities in a two-stage continuous culture system. Appl. Environ. Microbiol. 71, 7483–7492 (2005).

60 Kashyap, P. C. et al. Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota. Proc. Natl Acad. Sci. USA 110, 17059–17064 (2013).

61 Kelly, R. J., Rouquier, S., Giorgi, D., Lennon, G. G. & Lowe, J. B. Sequence and expression of a candidate for the human Secretor blood group alpha(1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J. Biol. Chem. 270, 4640–4649 (1995).

62 Lindesmith, L. et al. Human susceptibility and resistance to Norwalk virus infection. Nat. Med. 9, 548–553 (2003).

63 Chaudhuri, A. & DasAdhikary, C. R. Possible role of blood-group secretory substances in the aetiology of cholera. Trans. R. Soc. Trop. Med. Hyg. 72, 664–665 (1978).

64 Ruiz-Palacios, G. M., Cervantes, L. E., Ramos, P., Chavez-Munguia, B. & Newburg, D. S. Campylobacter jejuni binds intestinal H(O) antigen (Fuc alpha 1, 2Gal beta 1, 4GlcNAc), and fucosyloligosaccharides of human milk inhibit its binding and infection. J. Biol. Chem. 278, 14112–14120 (2003).

65 Ikehara, Y. et al. Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes) involving type I Lewis antigens are associated with the presence of anti-Helicobacter pylori IgG antibody. Cancer Epidemiol. Biomarkers Prev. 10, 971–977 (2001).

66 Folseraas, T. et al. Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. J. Hepatol. 57, 366–375 (2012).

67 Smyth, D. J. et al. FUT2 nonsecretor status links type 1 diabetes susceptibility and resistance to infection. Diabetes 60, 3081–3084 (2011).

68 Parmar, A. S. et al. Association study of FUT2 (rs601338) with celiac disease and inflammatory bowel disease in the Finnish population. Tissue Antigens 80, 488–493 (2012).

69 Tong, M. et al. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism. ISME J. 8, 2193–2206 (2014).

70 Frank, D. N. et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc. Natl Acad. Sci. USA 104, 13780–13785 (2007).

71 Comstock, L. E. et al. Analysis of a capsular polysaccharide biosynthesis locus of Bacteroides fragilis. Infect. Immun. 67, 3525–3532 (1999).

72 Coyne, M. J., Reinap, B., Lee, M. M. & Comstock, L. E. Human symbionts use a host-like pathway for surface fucosylation. Science 307, 1778–1781 (2005).

73 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).

74 Tailford, L. E., Crost, E. H., Kavanaugh, D. & Juge, N. Mucin glycan foraging in the human gut microbiome. Front. Genet. 6, 81 (2015).

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

76 Tishkoff, S. A. et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat. Genet. 39, 31–40 (2007).

77 Azcarate-Peril, M. A. et al. Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals. Proc. Natl Acad. Sci. USA 114, E367–E375 (2017).

78 Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013). This study reports the transfer of gut microbiota from twins discordant for obesity to germ-free mice. Mice that received gut microbiota from the obese twin accumulated more fat.

79 Beaumont, M. et al. Heritable components of the human fecal microbiome are associated with visceral fat. Genome Biol. 17, 189 (2016).

80 Million, M. et al. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int. J. Obes. (Lond.) 37, 1460–1466 (2013).

81 Lahti, L. et al. Associations between the human intestinal microbiota. Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data. PeerJ 1, e32 (2013).

82 Chen, J., Chen, L., Sanseau, P., Freudenberg, J. M. & Rajpal, D. K. Significant obesity-associated gene expression changes occur in the stomach but not intestines in obese mice. Physiol. Rep. 4, e12793 (2016).

83 Juan-Mateu, J. et al. Neuron-enriched RNA-binding proteins regulate pancreatic beta cell function and survival. J. Biol. Chem. 292, 3466–3480 (2017).

84 Speakman, J. R. Functional analysis of seven genes linked to body mass index and adiposity by genome-wide association studies: a review. Hum. Hered. 75, 57–79 (2013).

85 Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA 110, 9066–9071 (2013).

86 Derrien, M., Vaughan, E. E., Plugge, C. M. & de Vos, W. M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol. 54, 1469–1476 (2004).

87 Collado, M. C., Derrien, M., Isolauri, E., de Vos, W. M. & Salminen, S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl. Environ. Microbiol. 73, 7767–7770 (2007).

88 Derrien, M., Collado, M. C., Ben-Amor, K., Salminen, S. & de Vos, W. M. The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl. Environ. Microbiol. 74, 1646–1648 (2008).

89 van Passel, M. W. et al. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS ONE 6, e16876 (2011).

90 Walley, A. J. et al. Differential coexpression analysis of obesity-associated networks in human subcutaneous adipose tissue. Int. J. Obes. (Lond.) 36, 137–147 (2012).

91 Ng, M. C. et al. Genome-wide association of BMI in African Americans. Obes. (Silver Spring) 20, 622–627 (2012).

92 Cassese, A. et al. Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15. PLoS ONE 8, e60555 (2013).

93 Org, E. et al. Genetic and environmental control of host-gut microbiota interactions. Genome Res. 25, 1558–1569 (2015).

94 Greer, R. L. et al. Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism. Nat. Commun. 7, 13329 (2016).

95 Eriksson, N. et al. A genetic variant near olfactory receptor genes influences cilantro preference. Flavour 1, 1–7 (2012).

96 Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 15, 382–392 (2014).

97 Weiser, M. et al. Molecular classification of Crohn's disease reveals two clinically relevant subtypes. Gut http://dx.doi.org/10.1136/gutjnl-2016-312518 (2016).

98 Mahmood, S. S., Levy, D., Vasan, R. S. & Wang, T. J. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. Lancet 383, 999–1008 (2014).

99 Group, T. S. The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr. Diabetes 8, 286–298 (2007).

100 Shungin, D. et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature 518, 187–196 (2015).

101 David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014). In this study, participants were fed a plant-based or animal-based diet for 5 days; the results revealed that diet is a major influence on the composition of the gut microbiota.

102 Carmody, R. N. et al. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe 17, 72–84 (2015).

103 Smillie, C. S. et al. Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480, 241–244 (2011).

104 Segata, N. et al. Metagenomic microbial community profiling using unique clade-specific marker genes. Nat. Methods 9, 811–814 (2012).

105 Abubucker, S. et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput. Biol. 8, e1002358 (2012).

106 Yassour, M. et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci. Transl. Med. 8, 343ra381 (2016).

107 Saraswati, S. & Sitaraman, R. Aging and the human gut microbiota-from correlation to causality. Front. Microbiol. 5, 764 (2014).

108 Rodriguez, J. M. et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb. Ecol. Health Dis. 26, 26050 (2015).

109 Rolhion, N. & Darfeuille-Michaud, A. Adherent-invasive Escherichia coli in inflammatory bowel disease. Inflamm. Bowel Dis. 13, 1277–1283 (2007).