Over the past few years, microbiome research has dramatically reshaped our understanding of human biology. New insights range from an enhanced understanding of how microbes mediate digestion and disease processes (e.g., in inflammatory bowel disease) to surprising associations with Parkinson's disease, autism, and depression. In this review, we describe how new generations of sequencing technology, analytical advances coupled to new software capabilities, and the integration of animal model data have led to these new discoveries. We also discuss the prospects for integrating studies of the microbiome, metabolome, and immune system, with the goal of elucidating mechanisms that govern their interactions. This systems-level understanding will change how we think about ourselves as organisms.


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Literature Cited

  1. Aagaard KM. 1.  2014. Author response to comment on “The placenta harbors a unique microbiome.”. Sci. Transl. Med. 6:254lr3 [Google Scholar]
  2. Aagaard KM, Riehle K, Ma J, Segata N, Mistretta T-A. 2.  et al. 2012. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLOS ONE 7:e36466 [Google Scholar]
  3. Alekseyenko AV, Perez-Perez GI, De Souza A, Strober B, Gao Z. 3.  et al. 2013. Community differentiation of the cutaneous microbiota in psoriasis. Microbiome 1:31 [Google Scholar]
  4. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 4.  1990. Basic local alignment search tool. J. Mol. Biol. 215:403–10 [Google Scholar]
  5. Aminov RI. 5.  2010. A brief history of the antibiotic era: lessons learned and challenges for the future. Front. Microbiol. 1:134 [Google Scholar]
  6. Amir A, McDonald D, Navas-Molina JA, Kopylova E, Morton JT. 6.  et al. 2017. Deblur rapidly resolves single-nucleotide community sequence patterns. mSystems 2:e00191-16 [Google Scholar]
  7. Anderson MJ. 7.  2001. A new method for non-parametric multivariate analysis of variance. Aust. Ecol. 26:32–46 [Google Scholar]
  8. Arrieta M-C, Stiemsma LT, Dimitriu PA, Thorson L, Russell S. 8.  et al. 2015. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci. Transl. Med. 7:307ra152 [Google Scholar]
  9. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T. 9.  et al. 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–41 [Google Scholar]
  10. Azad MB, Bridgman SL, Becker AB, Kozyrskyj AL. 10.  2014. Infant antibiotic exposure and the development of childhood overweight and central adiposity. Int. J. Obes. 38:1290–98 [Google Scholar]
  11. Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H. 11.  et al. 2015. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17:690–703 [Google Scholar]
  12. Bartlett JG, Gerding DN. 12.  2008. Clinical recognition and diagnosis of Clostridium difficile infection. Clin. Infect. Dis. 46:Suppl. 1S12–18 [Google Scholar]
  13. Baum BR. 13.  1989. PHYLIP: Phylogeny Inference Package. Version 3.2. Q. Rev. Biol. 64:539–41 [Google Scholar]
  14. Benedict C, Vogel H, Jonas W, Woting A, Blaut M. 14.  et al. 2016. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals. Mol. Metab. 5:1175–86 [Google Scholar]
  15. Bergey DH, Brown CP, Etris S. 15.  1939. Immunization against tetanus with alum-precipitated tetanus toxoid. Am. J. Public Health Nations Health 29:334–36 [Google Scholar]
  16. Bessa LJ, Fazii P, Di Giulio M, Cellini L. 16.  2015. Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: some remarks about wound infection. Int. Wound J. 12:47–52 [Google Scholar]
  17. Binladen J, Gilbert MTP, Bollback JP, Panitz F, Bendixen C. 17.  et al. 2007. The use of coded PCR primers enables high-throughput sequencing of multiple homolog amplification products by 454 parallel sequencing. PLOS ONE 2:e197 [Google Scholar]
  18. Bond PL, Hugenholtz P, Keller J, Blackall LL. 18.  1995. Bacterial community structures of phosphate-removing and non-phosphate-removing activated sludges from sequencing batch reactors. Appl. Environ. Microbiol. 61:1910–16 [Google Scholar]
  19. Bouslimani A, Porto C, Rath CM, Wang M, Guo Y. 19.  et al. 2015. Molecular cartography of the human skin surface in 3D. PNAS 112:E2120–19 [Google Scholar]
  20. Bray JR, Curtis JT. 20.  1957. An ordination of the upland forest communities of southern Wisconsin. Ecol. Monogr. 27:325–49 [Google Scholar]
  21. Brosius J, Palmer ML, Kennedy PJ, Noller HF. 21.  1978. Complete nucleotide sequence of a 16S ribosomal RNA gene from Escherichia coli. PNAS 75:4801–5 [Google Scholar]
  22. Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. 22.  2012. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am. J. Clin. Nutr. 96:544–51 [Google Scholar]
  23. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. 23.  2016. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13:581–83 [Google Scholar]
  24. 24. Cambies. 1949. Parodontose et cure thermale. Rev. Odontol. 71:447–52 [Google Scholar]
  25. Campbell SC, Wisniewski PJ. 25.  2017. Exercise is a novel promoter of intestinal health and microbial diversity. Exerc. Sport Sci. Rev. 45:41–47 [Google Scholar]
  26. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD. 26.  et al. 2010. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7:335–36 [Google Scholar]
  27. Charbonneau MR, O'Donnell D, Blanton LV, Totten SM, Davis JCC. 27.  et al. 2016. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell 164:859–71 [Google Scholar]
  28. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S. 28.  et al. 2015. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519:92–96 [Google Scholar]
  29. Clayton TA, Baker D, Lindon JC, Everett JR, Nicholson JK. 29.  2009. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. PNAS 106:14728–33 [Google Scholar]
  30. Coppa GV, Gabrielli O, Pierani P, Catassi C, Carlucci A, Giorgi PL. 30.  1993. Changes in carbohydrate composition in human milk over 4 months of lactation. Pediatrics 91:637–41 [Google Scholar]
  31. Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. 31.  2009. Bacterial community variation in human body habitats across space and time. Science 326:1694–97 [Google Scholar]
  32. David LA, Materna AC, Friedman J, Campos-Baptista MI, Blackburn MC. 32.  et al. 2014. Host lifestyle affects human microbiota on daily timescales. Genome Biol 15:R89 [Google Scholar]
  33. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE. 33.  et al. 2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–63 [Google Scholar]
  34. Debelius J, Song SJ, Vazquez-Baeza Y, Xu ZZ, Gonzalez A, Knight R. 34.  2016. Tiny microbes, enormous impacts: What matters in gut microbiome studies?. Genome Biol 17:217 [Google Scholar]
  35. Dethlefsen L, Relman DA. 35.  2011. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. PNAS 108:Suppl.4554–61 [Google Scholar]
  36. Diaz Heijtz R, Wang S, Anuar F, Qian Y, Björkholm B. 36.  et al. 2011. Normal gut microbiota modulates brain development and behavior. PNAS 108:3047–52 [Google Scholar]
  37. Ding HT, Taur Y, Walkup JT. 37.  2017. Gut microbiota and autism: key concepts and findings. J. Autism Dev. Disord. 47:480–89 [Google Scholar]
  38. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G. 38.  et al. 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. PNAS 107:11971–75 [Google Scholar]
  39. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L. 39.  et al. 2005. Diversity of the human intestinal microbial flora. Science 308:1635–38 [Google Scholar]
  40. Elwood HJ, Olsen GJ, Sogin ML. 40.  1985. The small-subunit ribosomal RNA gene sequences from the hypotrichous ciliates Oxytricha nova. Stylonychia pustulata. Mol. Biol. Evol. 2:399–410 [Google Scholar]
  41. Eren AM, Maignien L, Sul WJ, Murphy LG, Grim SL. 41.  et al. 2013. Oligotyping: differentiating between closely related microbial taxa using 16S rRNA gene data. Methods Ecol. Evol. 4:1111–19 [Google Scholar]
  42. Eren AM, Morrison HG, Lescault PJ, Reveillaud J, Vineis JH, Sogin ML. 42.  2015. Minimum entropy decomposition: unsupervised oligotyping for sensitive partitioning of high-throughput marker gene sequences. ISME J 9:968–79 [Google Scholar]
  43. Fierer N, Lauber CL, Zhou N, McDonald D, Costello EK, Knight R. 43.  2010. Forensic identification using skin bacterial communities. PNAS 107:6477–81 [Google Scholar]
  44. Fitz-Gibbon S, Tomida S, Chiu B-H, Nguyen L, Du C. 44.  et al. 2013. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J. Investig. Dermatol. 133:2152–60 [Google Scholar]
  45. Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E. 45.  et al. 2015. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:262–66 [Google Scholar]
  46. Fouhy F, Guinane CM, Hussey S, Wall R, Ryan CA. 46.  et al. 2012. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob. Agents Chemother. 56:5811–20 [Google Scholar]
  47. Francino MP. 47.  2015. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front. Microbiol. 6:1543 [Google Scholar]
  48. Franzosa EA, Huang K, Meadow JF, Gevers D, Lemon KP. 48.  et al. 2015. Identifying personal microbiomes using metagenomic codes. PNAS 112:E2930–38 [Google Scholar]
  49. Fredricks DN, Fiedler TL, Marrazzo JM. 49.  2005. Molecular identification of bacteria associated with bacterial vaginosis. N. Engl. J. Med. 353:1899–911 [Google Scholar]
  50. Gao R, Gao Z, Huang L, Qin H. 50.  2017. Gut microbiota and colorectal cancer. Eur. J. Clin. Microbiol. Infect. Dis. 36:757–69 [Google Scholar]
  51. Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W. 51.  et al. 2014. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 15:382–92 [Google Scholar]
  52. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ. 52.  et al. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312:1355–59 [Google Scholar]
  53. Girard C, Tromas N, Amyot M, Shapiro BJ. 53.  2017. Gut microbiome of the Canadian Arctic Inuit. mSphere 2:e00297–16 [Google Scholar]
  54. Gonzalez A, Stombaugh J, Lauber CL, Fierer N, Knight R. 54.  2012. SitePainter: a tool for exploring biogeographical patterns. Bioinformatics 28:436–38 [Google Scholar]
  55. Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O. 55.  et al. 2014. Human genetics shape the gut microbiome. Cell 159:789–99 [Google Scholar]
  56. Hamady M, Walker JJ, Harris JK, Gold NJ, Knight R. 56.  2008. Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex. Nat. Methods 5:235–37 [Google Scholar]
  57. Harris RA, Shah R, Hollister EB, Tronstad RR, Hovdenak N. 57.  et al. 2016. Colonic mucosal epigenome and microbiome development in children and adolescents. J. Immunol. Res 2016:9170162 [Google Scholar]
  58. Hartmann P, Seebauer CT, Schnabl B. 58.  2015. Alcoholic liver disease: the gut microbiome and liver cross talk. Alcohol. Clin. Exp. Res. 39:763–75 [Google Scholar]
  59. Hernandez CJ, Guss JD, Luna M, Goldring SR. 59.  2016. Links between the microbiome and bone. J. Bone Miner. Res. 31:1638–46 [Google Scholar]
  60. Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS. 60.  et al. (Bact. Vaginosis Prematur. Study Group). 1995. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. N. Engl. J. Med 333:1737–42 [Google Scholar]
  61. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER. 61.  et al. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155:1451–63 [Google Scholar]
  62. Huber JA, Mark Welch DB, Morrison HG, Huse SM, Neal PR. 62.  et al. 2007. Microbial population structures in the deep marine biosphere. Science 318:97–100 [Google Scholar]
  63. 63. Hum. Microbiome Proj. Consort. 2012. A framework for human microbiome research. Nature 486:215–21 [Google Scholar]
  64. 64. Hum. Microbiome Proj. Consort. 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:207–14 [Google Scholar]
  65. Huse SM, Huber JA, Morrison HG, Sogin ML, Mark Welch DB. 65.  2007. Accuracy and quality of massively parallel DNA pyrosequencing. Genome Biol 8:R143 [Google Scholar]
  66. Huse SM, Mark Welch DB, Voorhis A, Shipunova A, Morrison HG. 65a.  2014. VAMPS: a website for visualization and analysis of microbial population structures. BMC Bioinform 15:41 [Google Scholar]
  67. Hviid A, Svanstrom H, Frisch M. 66.  2011. Antibiotic use and inflammatory bowel diseases in childhood. Gut 60:49–54 [Google Scholar]
  68. Inan MS, Rasoulpour RJ, Yin L, Hubbard AK, Rosenberg DW, Giardina C. 67.  2000. The luminal short-chain fatty acid butyrate modulates NF-κB activity in a human colonic epithelial cell line. Gastroenterology 118:724–34 [Google Scholar]
  69. Jakobsson HE, Jernberg C, Andersson AF, Sjölund-Karlsson M, Jansson JK, Engstrand L. 68.  2010. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLOS ONE 5:e9836 [Google Scholar]
  70. Jangi S, Gandhi R, Cox LM, Li N, von Glehn F. 69.  et al. 2016. Alterations of the human gut microbiome in multiple sclerosis. Nat. Commun. 7:12015 [Google Scholar]
  71. Jonsson AL, Bäckhed F. 70.  2017. Role of gut microbiota in atherosclerosis. Nat. Rev. Cardiol. 14:79–87 [Google Scholar]
  72. Kane AV, Dinh DM, Ward HD. 71.  2015. Childhood malnutrition and the intestinal microbiome. Pediatr. Res. 77:256–62 [Google Scholar]
  73. Kilkkinen A, Virtanen SM, Klaukka T, Kenward MG, Salkinoja-Salonen M. 72.  et al. 2006. Use of antimicrobials and risk of type 1 diabetes in a population-based mother-child cohort. Diabetologia 49:66–70 [Google Scholar]
  74. Kiraly DD, Walker DM, Calipari ES, Labonte B, Issler O. 73.  et al. 2016. Alterations of the host microbiome affect behavioral responses to cocaine. Sci. Rep. 6:35455 [Google Scholar]
  75. Kleiman SC, Watson HJ, Bulik-Sullivan EC, Huh EY, Tarantino LM. 74.  et al. 2015. The intestinal microbiota in acute anorexia nervosa and during renourishment: relationship to depression, anxiety, and eating disorder psychopathology. Psychosom. Med. 77:969–81 [Google Scholar]
  76. Kliman HJ. 75.  2014. Comment on “The placenta harbors a unique microbiome. .” Sci. Transl. Med. 6:254le4 [Google Scholar]
  77. Knights D, Lassen KG, Xavier RJ. 76.  2013. Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome. Gut 62:1505–10 [Google Scholar]
  78. Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H. 77.  et al. 2015. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity 42:756–66 [Google Scholar]
  79. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J. 78.  et al. 2011. Succession of microbial consortia in the developing infant gut microbiome. PNAS 108:Suppl.4578–85 [Google Scholar]
  80. Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K. 79.  et al. 2012. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150:470–80 [Google Scholar]
  81. Kostic AD, Gevers D, Siljander H, Vatanen T, Hyötyläinen T. 80.  et al. 2015. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17:260–73 [Google Scholar]
  82. Kostic AD, Xavier RJ, Gevers D. 81.  2014. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 146:1489–99 [Google Scholar]
  83. Kuczynski J, Liu Z, Lozupone CA, McDonald D, Fierer N, Knight R. 82.  2010. Microbial community resemblance methods differ in their ability to detect biologically relevant patterns. Nat. Methods 7:813–19 [Google Scholar]
  84. Kutty N. 83.  2011. Treating children without antibiotics in primary healthcare. Oman Med. J 26:303–5 [Google Scholar]
  85. Kwak M-J, Kwon S-K, Yoon J-K, Song JY, Seo J-G. 84.  et al. 2016. Evolutionary architecture of the infant-adapted group of Bifidobacterium species associated with the probiotic function. Syst. Appl. Microbiol. 39:429–39 [Google Scholar]
  86. Lane DJ, Pace B, Olsen GJ, Stahl DA, Sogin ML, Pace NR. 85.  1985. Rapid determination of 16S ribosomal RNA sequences for phylogenetic analyses. PNAS 82:6955–59 [Google Scholar]
  87. Lauder AP, Roche AM, Sherrill-Mix S, Bailey A, Laughlin AL. 86.  et al. 2016. Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. Microbiome 4:29 [Google Scholar]
  88. Lax S, Smith DP, Hampton-Marcell J, Owens SM, Handley KM. 87.  et al. 2014. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science 345:1048–52 [Google Scholar]
  89. Ley RE, Hamady M, Lozupone CA, Turnbaugh PJ, Ramey RR. 88.  et al. 2008. Evolution of mammals and their gut microbes. Science 320:1647–51 [Google Scholar]
  90. Ley RE, Lozupone CA, Hamady M, Knight R, Gordon JI. 89.  2008. Worlds within worlds: evolution of the vertebrate gut microbiota. Nat. Rev. Microbiol. 6:776–88 [Google Scholar]
  91. Li J, Jia H, Cai X, Zhong H, Feng Q. 90.  et al. 2014. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32:834–41 [Google Scholar]
  92. Liu Z, DeSantis TZ, Andersen GL, Knight R. 91.  2008. Accurate taxonomy assignments from 16S rRNA sequences produced by highly parallel pyrosequencers. Nucleic Acids Res 36:e120 [Google Scholar]
  93. Liu Z, Lozupone CA, Hamady M, Bushman FD, Knight R. 92.  2007. Short pyrosequencing reads suffice for accurate microbial community analysis. Nucleic Acids Res 35:e120 [Google Scholar]
  94. Lowry CA, Smith DG, Siebler PH, Schmidt D, Stamper CE. 93.  et al. 2016. The microbiota, immunoregulation, and mental health: implications for public health. Curr. Environ. Heal. Rep. 3:270–86 [Google Scholar]
  95. Lozupone CA, Knight R. 94.  2005. UniFrac: a new phylogenetic method for comparing microbial communities. Appl. Environ. Microbiol. 71:8228–35 [Google Scholar]
  96. Lozupone CA, Knight R. 95.  2007. Global patterns in bacterial diversity. PNAS 104:11436–40 [Google Scholar]
  97. Ludwig W, Strunk O, Westram R, Richter L, Meier H. 96.  et al. 2004. ARB: a software environment for sequence data. Nucleic Acids Res 32:1363–71 [Google Scholar]
  98. Lynch SV, Bruce KD. 97.  2013. The cystic fibrosis airway microbiome. Cold Spring Harb. Perspect. Med. 3:a009738 [Google Scholar]
  99. MacIntyre DA, Chandiramani M, Lee YS, Kindinger L, Smith A. 98.  et al. 2015. The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci. Rep. 5:8988 [Google Scholar]
  100. Makrides M, Simmer K, Neumann M, Gibson R. 99.  1995. Changes in the polyunsaturated fatty acids of breast milk from mothers of full-term infants over 30 wk of lactation. Am. J. Clin. Nutr. 61:1231–33 [Google Scholar]
  101. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS. 100.  et al. 2005. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437:376–80 [Google Scholar]
  102. Maurice CF, Haiser HJ, Turnbaugh PJ. 101.  2013. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152:39–50 [Google Scholar]
  103. Maxam AM, Gilbert W. 102.  1977. A new method for sequencing DNA. PNAS 74:560–64 [Google Scholar]
  104. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. 103.  2005. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122:107–18 [Google Scholar]
  105. McCaig AE, Glover LA, Prosser JI. 104.  1999. Molecular analysis of bacterial community structure and diversity in unimproved and improved upland grass pastures. Appl. Environ. Microbiol. 65:1721–30 [Google Scholar]
  106. McNulty NP, Yatsunenko T, Hsiao A, Faith JJ, Muegge BD. 105.  et al. 2011. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci. Transl. Med. 3:106ra106 [Google Scholar]
  107. Medlin L, Elwood HJ, Stickel S, Sogin ML. 106.  1988. The characterization of enzymatically amplified eukaryotic 16S-like rRNA-coding regions. Gene 71:491–99 [Google Scholar]
  108. Metcalf JL, Xu ZZ, Weiss S, Lax S, Van Treuren W. 107.  et al. 2016. Microbial community assembly and metabolic function during mammalian corpse decomposition. Science 351:158–62 [Google Scholar]
  109. Metsälä J, Lundqvist A, Virta LJ, Kaila M, Gissler M, Virtanen SM. 108.  2013. Mother's and offspring's use of antibiotics and infant allergy to cow's milk. Epidemiology 24:303–9 [Google Scholar]
  110. Miller JB, Bull S, Miller J, McVeagh P. 109.  1994. The oligosaccharide composition of human milk: temporal and individual variations in monosaccharide components. J. Pediatr. Gastroenterol. Nutr. 19:371–76 [Google Scholar]
  111. Mimouna S, Gonçalvès D, Barnich N, Darfeuille-Michaud A, Hofman P, Vouret-Craviari V. 110.  2011. Crohn disease-associated Escherichia coli promote gastrointestinal inflammatory disorders by activation of HIF-dependent responses. Gut Microbes 2:335–46 [Google Scholar]
  112. Moeller AH, Caro-Quintero A, Mjungu D, Georgiev AV, Lonsdorf EV. 111.  et al. 2016. Cospeciation of gut microbiota with hominids. Science 353:380–82 [Google Scholar]
  113. Moeller AH, Peeters M, Ndjango J-B, Li Y, Hahn BH, Ochman H. 112.  2013. Sympatric chimpanzees and gorillas harbor convergent gut microbial communities. Genome Res 23:1715–20 [Google Scholar]
  114. Mohr JL. 113.  1952. Protozoa as indicators of pollution. Sci. Mon. 74:7–9 [Google Scholar]
  115. Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL. 114.  et al. 2012. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13:R79 [Google Scholar]
  116. Muegge BD, Kuczynski J, Knights D, Clemente JC, Gonzalez A. 115.  et al. 2011. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332:970–74 [Google Scholar]
  117. Niehues H, Schalkwijk J, van Vlijmen-Willems IMJJ, Rodijk-Olthuis D, van Rossum MM. 116.  et al. 2017. Epidermal equivalents of filaggrin null keratinocytes do not show impaired skin barrier function. J. Allergy Clin. Immunol. 139:1979–81.e13 [Google Scholar]
  118. Nobel YR, Cox LM, Kirigin FF, Bokulich NA, Yamanishi S. 117.  et al. 2015. Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment. Nat. Commun. 6:7486 [Google Scholar]
  119. Ochman H, Worobey M, Kuo C-H, Ndjango J-BN, Peeters M. 118.  et al. 2010. Evolutionary relationships of wild hominids recapitulated by gut microbial communities. PLOS BIOL 8:e1000546 [Google Scholar]
  120. Oliver A, Cantón R, Campo P, Baquero F, Blázquez J. 119.  2000. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:1251–54 [Google Scholar]
  121. Olm MR, Brown CT, Brooks B, Firek B, Baker R. 120.  et al. 2017. Identical bacterial populations colonize premature infant gut, skin, and oral microbiomes and exhibit different in situ growth rates. Genome Res 27:601–12 [Google Scholar]
  122. Olsen GJ, Overbeek R, Larsen N, Marsh TL, McCaughey MJ. 121.  et al. 1992. The ribosomal database project. Nucleic Acids Res 20:Suppl.2199–200 [Google Scholar]
  123. Pace B, Campbell LL. 122.  1971. Homology of ribosomal ribonucleic acid diverse bacterial species with Escherichia coli and Bacillus stearothermophilus. . J. Bacteriol. 107:543–47 [Google Scholar]
  124. Pace NR. 123.  1997. A molecular view of microbial diversity and the biosphere. Science 276:734–40 [Google Scholar]
  125. Paun A, Yau C, Danska JS. 124.  2017. The influence of the microbiome on type 1 diabetes. J. Immunol. 198:590–95 [Google Scholar]
  126. Peterson SN, Snesrud E, Liu J, Ong AC, Kilian M. 125.  et al. 2013. The dental plaque microbiome in health and disease. PLOS ONE 8:e58487 [Google Scholar]
  127. Prince AL, Ma J, Kannan PS, Alvarez M, Gisslen T. 126.  et al. 2016. The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis. Am. J. Obstet. Gynecol. 214:627.e1–16 [Google Scholar]
  128. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS. 127.  et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65 [Google Scholar]
  129. Quince C, Lanzen A, Curtis TP, Davenport RJ, Hall N. 128.  et al. 2009. Accurate determination of microbial diversity from 454 pyrosequencing data. Nat. Methods 6:639–41 [Google Scholar]
  130. Quinn RA, Lim YW, Maughan H, Conrad D, Rohwer F, Whiteson KL. 129.  2014. Biogeochemical forces shape the composition and physiology of polymicrobial communities in the cystic fibrosis lung. mBio 5:e00956–13 [Google Scholar]
  131. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS. 130.  et al. 2011. Vaginal microbiome of reproductive-age women. PNAS 108:Suppl.4680–87 [Google Scholar]
  132. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE. 131.  et al. 2013. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341:1241214 [Google Scholar]
  133. Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW. 132.  et al. 2014. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome 2:4 [Google Scholar]
  134. Round JL, Mazmanian SK. 133.  2009. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9:313–23 [Google Scholar]
  135. Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG. 134.  et al. 2016. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell 167:1469–80.e12 [Google Scholar]
  136. Sanger F, Nicklen S, Coulson AR. 135.  1977. DNA sequencing with chain-terminating inhibitors. PNAS 74:5463–67 [Google Scholar]
  137. Schloss PD, Handelsman J. 136.  2005. Introducing DOTUR, a computer program for defining operational taxonomic units and estimating species richness. Appl. Environ. Microbiol. 71:1501–6 [Google Scholar]
  138. Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M. 137.  et al. 2009. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 75:7537–41 [Google Scholar]
  139. Seedorf H, Griffin NW, Ridaura VK, Reyes A, Cheng J. 138.  et al. 2014. Bacteria from diverse habitats colonize and compete in the mouse gut. Cell 159:253–66 [Google Scholar]
  140. Sender R, Fuchs S, Milo R. 139.  2016. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164:337–40 [Google Scholar]
  141. Shulman JM, De Jager PL, Feany MB. 140.  2011. Parkinson's disease: genetics and pathogenesis. Annu. Rev. Pathol. Mech. Dis. 6:193–222 [Google Scholar]
  142. Simrén M, Barbara G, Flint HJ, Spiegel BMR, Spiller RC. 141.  et al. 2013. Intestinal microbiota in functional bowel disorders: a Rome Foundation report. Gut 62:159–76 [Google Scholar]
  143. Smith LM, Sanders JZ, Kaiser RJ, Hughes P, Dodd C. 142.  et al. 1986. Fluorescence detection in automated DNA sequence analysis. Nature 321:674–79 [Google Scholar]
  144. Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R. 143.  et al. 2013. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339:548–54 [Google Scholar]
  145. Sogin ML, Morrison HG, Huber JA, Mark Welch D, Huse SM. 144.  et al. 2006. Microbial diversity in the deep sea and the underexplored “rare biosphere.”. PNAS 103:12115–20 [Google Scholar]
  146. Sogin SJ, Sogin ML, Woese CR. 145.  1971. Phylogenetic measurement in procaryotes by primary structural characterization. J. Mol. Evol. 1:173–84 [Google Scholar]
  147. Song SJ, Lauber C, Costello EK, Lozupone CA, Humphrey G. 146.  et al. 2013. Cohabiting family members share microbiota with one another and with their dogs. eLife 2:e00458 [Google Scholar]
  148. Stanier RY, Van Niel CB. 147.  1941. The main outlines of bacterial classification. J. Bacteriol. 42:437–66 [Google Scholar]
  149. Steele JA, Countway PD, Xia L, Vigil PD, Beman JM. 148.  et al. 2011. Marine bacterial, archaeal and protistan association networks reveal ecological linkages. ISME J 5:1414–25 [Google Scholar]
  150. Stein MM, Hrusch CL, Gozdz J, Igartua C, Pivniouk V. 149.  et al. 2016. Innate immunity and asthma risk in Amish and Hutterite farm children. N. Engl. J. Med. 375:411–21 [Google Scholar]
  151. Subramanian S, Huq S, Yatsunenko T, Haque R, Mahfuz M. 150.  et al. 2014. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510:417–21 [Google Scholar]
  152. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA. 151.  et al. 2014. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514:181–86 [Google Scholar]
  153. Tang WHW, Hazen SL. 152.  2014. The contributory role of gut microbiota in cardiovascular disease. J. Clin. Investig. 124:4204–11 [Google Scholar]
  154. Thaiss CA, Zeevi D, Levy M, Zilberman-Schapira G, Suez J. 153.  et al. 2014. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 159:514–29 [Google Scholar]
  155. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A. 154.  et al. 2009. A core gut microbiome in obese and lean twins. Nature 457:480–84 [Google Scholar]
  156. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. 155.  2007. The Human Microbiome Project. Nature 449:804–10 [Google Scholar]
  157. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. 156.  2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–31 [Google Scholar]
  158. Wang X, Xu X, Xia Y. 157.  2017. Further analysis reveals new gut microbiome markers of type 2 diabetes mellitus. Antonie van Leeuwenhoek 110:445–53 [Google Scholar]
  159. Weingarden A, González A, Vázquez-Baeza Y, Weiss S, Humphry G. 158.  et al. 2015. Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. Microbiome 3:10 [Google Scholar]
  160. Woese CR. 159.  1987. Bacterial evolution. Microbiol. Rev. 51:221–71 [Google Scholar]
  161. Woese CR, Fox GE. 160.  1977. Phylogenetic structure of the prokaryotic domain: the primary kingdoms. PNAS 74:5088–90 [Google Scholar]
  162. Woese CR, Kandler O, Wheelis ML. 161.  1990. Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. PNAS 87:4576–79 [Google Scholar]
  163. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY. 162.  et al. 2011. Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105–8 [Google Scholar]
  164. Yang F, Zeng X, Ning K, Liu KL, Lo CC. 163.  et al. 2012. Saliva microbiomes distinguish caries-active from healthy human populations. ISME J 6:1–10 [Google Scholar]
  165. Yarza P, Yilmaz P, Pruesse E, Glöckner FO, Ludwig W. 164.  et al. 2014. Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences. Nat. Rev. Microbiol. 12:635–45 [Google Scholar]
  166. Yassour M, Vatanen T, Siljander H, Hämäläinen A-M, Härkönen T. 165.  et al. 2016. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci. Transl. Med. 8:343ra81 [Google Scholar]
  167. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG. 166.  et al. 2012. Human gut microbiome viewed across age and geography. Nature 486:222–27 [Google Scholar]
  168. Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D. 167.  et al. 2015. Personalized nutrition by prediction of glycemic responses. Cell 163:1079–94 [Google Scholar]
  169. Zhang X, Zhang D, Jia H, Feng Q, Wang D. 168.  et al. 2015. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med. 21:895–905 [Google Scholar]
  170. Zheng J, Xiao X, Zhang Q, Mao L, Yu M, Xu J. 169.  2015. The placental microbiome varies in association with low birth weight in full-term neonates. Nutrients 7:6924–37 [Google Scholar]
  171. Zheng P, Zeng B, Zhou C, Liu M, Fang Z. 170.  et al. 2016. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol. Psychiatry 21:786–96 [Google Scholar]
  172. Zozaya M, Ferris MJ, Siren JD, Lillis R, Myers L. 171.  et al. 2016. Bacterial communities in penile skin, male urethra, and vaginas of heterosexual couples with and without bacterial vaginosis. Microbiome 4:16 [Google Scholar]
  173. Zuckerkandl E, Pauling L. 172.  1965. Molecules as documents of evolutionary history. J. Theor. Biol. 8:357–66 [Google Scholar]

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