The human intestinal microbiome in health and disease

New England Journal of Medicine

Volumn 375, Issue 24, 2016, Pages 2369-2379

  Lynch, Susan V ^a   Pedersen, Oluf ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 10; INTERLEUKIN 4; PREBIOTIC AGENT; PROBIOTIC AGENT; SYNBIOTIC AGENT; TRIMETHYLAMINE OXIDE;

ATHEROSCLEROSIS; BACTERIAL GENOME; BACTEROIDES FRAGILIS; BIFIDOBACTERIUM; CALORIC RESTRICTION; CHRONIC DISEASE; CLOSTRIDIUM DIFFICILE INFECTION; COMMENSAL; CYTOKINE PRODUCTION; DYSBIOSIS; ESCHERICHIA COLI; FECAL MICROBIOTA TRANSPLANTATION; HIGH THROUGHPUT SEQUENCING; HUMAN; HUMAN GENOME; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; LACTOCOCCUS LACTIS; MACHINE LEARNING; MICROBIAL DIVERSITY; NONHUMAN; OBESITY; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; AGING; ANIMAL; BIOLOGICAL THERAPY; DIET; DISEASE; GASTROINTESTINAL TRACT; HEALTH; MICROBIOLOGY; PHYSIOLOGY;

AGING; ANIMALS; BIOLOGICAL THERAPY; DIET; DISEASE; FECAL MICROBIOTA TRANSPLANTATION; GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL TRACT; HEALTH; HUMANS;

EID: 85005965070     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMra1600266     Document Type: Review

References (112)

1. Staley JT, Konopka A. Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu Rev Microbiol 1985; 39: 321-46.
2. Oh J, Byrd AL, Deming C, Conlan S, Kong HH, Segre JA. Biogeography and individuality shape function in the human skin metagenome. Nature 2014; 514: 59- 64.
3. Li J, Jia H, Cai X, et al. An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol 2014; 32: 834-41.
4. Fulde M, Hornef MW. Maturation of the enteric mucosal innate immune system during the postnatal period. Immunol Rev 2014; 260: 21-34.
5. Kamada N, Chen GY, Inohara N, Núñez G. Control of pathogens and pathobionts by the gut microbiota. Nat Immunol 2013; 14: 685-90.
6. Ijssennagger N, Belzer C, Hooiveld GJ, et al. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon. Proc Natl Acad Sci U S A 2015; 112: 10038-43.
7. Reinhardt C, Bergentall M, Greiner TU, et al. Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling. Nature 2012; 483: 627-31.
8. Neuman H, Debelius JW, Knight R, Koren O. Microbial endocrinology: The interplay between the microbiota and the endocrine system. FEMS Microbiol Rev 2015; 39: 509-21.
9. Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 2015; 161: 264-76.
10. Cho I, Yamanishi S, Cox L, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 2012; 488: 621-6.
11. Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol 2015; 11: 577-91.
12. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature 2012; 486: 222-7.
13. Devlin AS, Fischbach MA. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat Chem Biol 2015; 11: 685-90.
14. Haiser HJ, Gootenberg DB, Chatman K, Sirasani G, Balskus EP, Turnbaugh PJ. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 2013; 341: 295-8.
15. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med 2014; 6: 237ra65.
16. DiGiulio DB, Romero R, Kusanovic JP, et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 2010; 64: 38-57.
17. Gosalbes MJ, Llop S, Vallès Y, Moya A, Ballester F, Francino MP. Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants. Clin Exp Allergy 2013; 43: 198-211.
18. Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 2010; 107: 11971-5.
19. Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015; 17: 852.
20. Martens EC, Chiang HC, Gordon JI. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 2008; 4: 447-57.
21. Cheng J, Ringel-Kulka T, Heikampde Jong I, et al. Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children. ISME J 2016; 10: 1002-14.
22. Hollister EB, Riehle K, Luna RA, et al. Structure and function of the healthy preadolescent pediatric gut microbiome. Microbiome 2015; 3: 36.
23. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science 2005; 308: 1635-8.
24. Reyes A, Haynes M, Hanson N, et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 2010; 466: 334-8.
25. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464: 59-65.
26. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486: 207-14.
27. Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012; 488: 178-84.
28. Zhernakova A, Kurilshikov A, Bonder MJ, et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 2016; 352: 565-9.
29. Falony G, Joossens M, Vieira-Silva S, et al. Population-level analysis of gut microbiome variation. Science 2016; 352: 560-4.
30. Goodrich JK, Waters JL, Poole AC, et al. Human genetics shape the gut microbiome. Cell 2014; 159: 789-99.
31. Wang S, Charbonnier LM, Noval Rivas M, et al. MyD88 adaptor-dependent microbial sensing by regulatory T cells promotes mucosal tolerance and enforces commensalism. Immunity 2015; 43: 289-303.
32. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505: 559-63.
33. Maurice CF, Haiser HJ, Turnbaugh PJ. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 2013; 152: 39-50.
34. Hsiao A, Ahmed AM, Subramanian S, et al. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection. Nature 2014; 515: 423-6.
35. Thaiss CA, Zeevi D, Levy M, et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 2014; 159: 514-29.
36. Fujimura KE, Demoor T, Rauch M, et al. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Proc Natl Acad Sci USA 2014; 111: 805-10.
37. Yallapragada SG, Nash CB, Robinson DT. Early-life exposure to antibiotics, alterations in the intestinal microbiome, and risk of metabolic disease in children and adults. Pediatr Ann 2015; 44(11): e265-9.
38. Johnson CC, Ownby DR, Alford SH, et al. Antibiotic exposure in early infancy and risk for childhood atopy. J Allergy Clin Immunol 2005; 115: 1218-24.
39. Beaumont M, Goodrich JK, Jackson MA, et al. Heritable components of the human fecal microbiome are associated with visceral fat. Genom Biol 2016; 17: 189.
40. Knights D, Silverberg MS, Weersma RK, et al. Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med 2014; 6: 107.
41. Fujimura KE, Sitarik AR, Havstad S, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med 2016; 22: 1187-91.
42. Zeevi D, Korem T, Zmora N, et al. Personalized nutrition by prediction of glycemic responses. Cell 2015; 163: 1079-94.
43. Fujimura KE, Johnson CC, Ownby DR, et al. Man's best friend? The effects of pet ownership on house dust microbial communities. J Allergy Clin Immunol 2010; 126(2): 410-2.e3.
44. Lynch SV, Wood RA, Boushey H, et al. Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. J Allergy Clin Immunol 2014; 134(3): 593-601.e12.
45. Stein MM, Hrusch CL, Gozdz J, et al. Innate immunity and asthma risk in Amish and Hutterite farm children. N Engl J Med 2016; 375: 411-21.
46. Ege MJ, Mayer M, Normand A-C, et al. Exposure to environmental microorganisms and childhood asthma. N Engl J Med 2011; 364: 701-9.
47. Vujkovic-Cvijin I, Dunham RM, Iwai S, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med 2013; 5: 193ra91.
48. Lozupone CA, Rhodes ME, Neff CP, Fontenot AP, Campbell TB, Palmer BE. HIV-induced alteration in gut microbiota: driving factors, consequences, and effects of antiretroviral therapy. Gut Microbes 2014; 5: 562-70.
49. Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: A new clinical frontier. Gut 2016; 65: 330-9.
50. Ha CW, Lam YY, Holmes AJ. Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health. World J Gastroenterol 2014; 20: 16498-517.
51. Walsh CJ, Guinane CM, O'Toole PW, Cotter PD. Beneficial modulation of the gut microbiota. FEBS Lett 2014; 588: 4120- 30.
52. Wang WL, Xu SY, Ren ZG, Tao L, Jiang JW, Zheng SS. Application of metagenomics in the human gut microbiome. World J Gastroenterol 2015; 21: 803-14.
53. Wu H, Tremaroli V, Bäckhed F. Linking microbiota to human diseases: A systems biology perspective. Trends Endocrinol Metab 2015; 26: 758-70.
54. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472: 57-63.
55. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of Lcarnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013; 19: 576-85.
56. Wilson Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368: 1575-84.
57. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature 2009; 457: 480-4.
58. Le Chatelier E, Nielsen T, Qin J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature 2013; 500: 541-6.
59. Qin J, Li Y, Cai Z, et al. A metagenome- wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490: 55-60.
60. Karlsson FH, Tremaroli V, Nookaew I, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013; 498: 99-103.
61. Arrieta MC, Stiemsma LT, Dimitriu PA, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med 2015; 7: 307ra152.
62. Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013; 155: 1451-63.
63. Langille MG, Zaneveld J, Caporaso JG, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 2013; 31: 814-21.
64. Nielsen HB, Almeida M, Juncker AS, et al. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat Biotechnol 2014; 32: 822-8.
65. Tremaroli V, Karlsson F, Werling M, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab 2015; 22: 228-38.
66. Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun 2015; 6: 6528.
67. Yu J, Feng Q, Wong SH, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 2015 September 25 (Epub ahead of print).
68. Zeller G, Tap J, Voigt AY, et al. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol 2014; 10: 766.
69. Zhang X, Zhang D, Jia H, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med 2015; 21: 895-905.
70. Cotillard A, Kennedy SP, Kong LC, et al. Dietary intervention impact on gut microbial gene richness. Nature 2013; 500: 585-8.
71. Qin N, Yang F, Li A, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 2014; 513: 59-64.
72. Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 2015; 528: 262-6.
73. Graessler J, Qin Y, Zhong H, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J 2013; 13: 514-22.
74. Karlsson FH, Fåk F, Nookaew I, et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun 2012; 3: 1245.
75. Sharon I, Morowitz MJ, Thomas BC, Costello EK, Relman DA, Banfield JF. Time series community genomics analysis reveals rapid shifts in bacterial species, strains, and phage during infant gut colonization. Genome Res 2013; 23: 111-20.
76. Ridaura VK, Faith JJ, Rey FE, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013; 341: 1241214.
77. Subramanian S, Huq S, Yatsunenko T, et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 2014; 510: 417-21.
78. Koren O, Goodrich JK, Cullender TC, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 2012; 150: 470-80.
79. Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 2016; 535: 376-81.
80. Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012; 143(4): 913-6.e7.
81. Hansen TH, Gøbel RJ, Hansen T, Pedersen O. The gut microbiome in cardiometabolic health. Genome Med 2015; 7: 33.
82. Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013; 108: 500-8.
83. Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis. J Crohns Colitis 2014; 8: 1569-81.
84. Lawley TD, Clare S, Walker AW, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog 2012; 8(10): e1002995.
85. Tvede M, Tinggaard M, Helms M. Rectal bacteriotherapy for recurrent Clostridium difficile-associated diarrhoea: results from a case series of 55 patients in Denmark 2000-2012. Clin Microbiol Infect 2015; 21: 48-53.
86. Wang Z, Roberts AB, Buffa JA, et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 2015; 163: 1585-95.
87. Cotter PD, Hill C, Ross RP. Bacteriocins: developing innate immunity for food. Nat Rev Microbiol 2005; 3: 777-88.
88. Lakshminarayanan B, Guinane CM, O'Connor PM, et al. Isolation and characterization of bacteriocin-producing bacteria from the intestinal microbiota of elderly Irish subjects. J Appl Microbiol 2013; 114: 886-98.
89. Buffie CG, Bucci V, Stein RR, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 2015; 517: 205-8.
90. Iida N, Dzutsev A, Stewart CA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 2013; 342: 967- 70.
91. Viaud S, Saccheri F, Mignot G, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 2013; 342: 971-6.
92. Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti- PD-L1 efficacy. Science 2015; 350: 1084-9.
93. Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015; 350: 1079-84.
94. Konichi H, Fujiya M, Tanaka H, et al. Probiotic-derived ferrichrome inhibits colon cancer progression via JNL-mediated apoptosis. Nat Commun 2016 August 10 (Epub ahead of print).
95. Cebula A, Seweryn M, Rempala GA, et al. Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota. Nature 2013; 497: 258-62.
96. Dasgupta S, Erturk-Hasdemir D, Ochoa-Reparaz J, Reinecker HC, Kasper DL. Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms. Cell Host Microbe 2014; 15: 413-23.
97. Atarashi K, Tanoue T, Oshima K, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013; 500: 232-6.
98. Ahern PP, Faith JJ, Gordon JI. Mining the human gut microbiota for effector strains that shape the immune system. Immunity 2014; 40: 815-23.
99. Braat H, Rottiers P, Hommes DW, et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol 2006; 4: 754-9.
100. Steidler L, Hans W, Schotte L, et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 2000; 289: 1352-5.
101. Marinho FA, Pacífico LG, Miyoshi A, et al. An intranasal administration of Lactococcus lactis strains expressing recombinant interleukin-10 modulates acute allergic airway inflammation in a murine model. Clin Exp Allergy 2010; 40: 1541-51.
102. Breton J, Tennoune N, Lucas N, et al. Gut commensal E. coli proteins activate host satiety pathways following nutrientinduced bacterial growth. Cell Metab 2016; 23: 324-34.
103. Westendorf AM, Gunzer F, Deppenmeier S, et al. Intestinal immunity of Escherichia coli NISSLE 1917: A safe carrier for therapeutic molecules. FEMS Immunol Med Microbiol 2005; 43: 373-84.
104. Chen Z, Guo L, Zhang Y, et al. Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity. J Clin Invest 2014; 124: 3391-406.
105. Duan F, Curtis KL, March JC. Secretion of insulinotropic proteins by commensal bacteria: rewiring the gut to treat diabetes. Appl Environ Microbiol 2008; 74: 7437-8.
106. Duan FF, Liu JH, March JC. Engineered commensal bacteria reprogram intestinal cells into glucose-responsive insulin-secreting cells for the treatment of diabetes. Diabetes 2015; 64: 1794-803.
107. Gerritsen J, Smidt H, Rijkers GT, de Vos WM. Intestinal microbiota in human health and disease: The impact of probiotics. Genes Nutr 2011; 6: 209-40.
108. Uusitalo U, Liu X, Yang J, et al. Association of early exposure of probiotics and islet autoimmunity in the TEDDY Study. JAMA Pediatr 2016; 170: 20-8.
109. Shoaie S, Ghaffari P, Kovatcheva- Datchary P, et al. Quantifying diet-induced metabolic changes of the human gut microbiome. Cell Metab 2015; 22: 320-31.
110. Macfarlane S, Cleary S, Bahrami B, Reynolds N, Macfarlane GT. Synbiotic consumption changes the metabolism and composition of the gut microbiota in older people and modifies inflammatory processes: A randomised, double-blind, placebo- controlled crossover study. Aliment Pharmacol Ther 2013; 38: 804-16.
111. Neef A, Sanz Y. Future for probiotic science in functional food and dietary supplement development. Curr Opin Clin Nutr Metab Care 2013; 16: 679-87.
112. Brahe LK, Le Chatelier E, Prifti E, et al. Dietary modulation of the gut microbiota - A randomised controlled trial in obese postmenopausal women. Br J Nutr 2015; 114: 406-17.