The gut microbiota and obesity: from correlation to causality

Journal name:
Nature Reviews Microbiology
Year published:
Published online


The gut microbiota has been linked with chronic diseases such as obesity in humans. However, the demonstration of causality between constituents of the microbiota and specific diseases remains an important challenge in the field. In this Opinion article, using Koch's postulates as a conceptual framework, I explore the chain of causation from alterations in the gut microbiota, particularly of the endotoxin-producing members, to the development of obesity in both rodents and humans. I then propose a strategy for identifying the causative agents of obesity in the human microbiota through a combination of microbiome-wide association studies, mechanistic analysis of host responses and the reproduction of diseases in gnotobiotic animals.

At a glance


  1. Human health is influenced by interactions among the gut microbiota, the host and the environment.
    Figure 1: Human health is influenced by interactions among the gut microbiota, the host and the environment.

    Humans are supraorganisms consisting of both human cells and microbial cells, particularly the gut microbiota. The gut microbiota interacts with host genetics and the environment (mainly diet) to influence the health of the human host. On the one hand, the gut microbiota releases toxins, such as lipopolysaccharides, and beneficial metabolites, such as vitamins and short-chain fatty acids, to damage or nourish humans, respectively. On the other hand, human genetics also imposes selective pressures on the gut microbiota through innate immunity or nutrient availability. The diet and particular drugs have a greater potential to shape the structure and function of the gut microbiota than host genetics, thus influencing the health state of the supraorganism.

  2. Strategy for demonstrating the causative role of the gut microbiota in chronic diseases.
    Figure 2: Strategy for demonstrating the causative role of the gut microbiota in chronic diseases.

    In order to screen all the potential key gut microbial phylotypes that might be associated with the aetiology or development of a specific chronic disease, a microbiome-wide association study should first be carried out. Either cross-sectional or longitudinal experiments can be involved, accompanied by time series and multisite sampling to obtain measurements of both host phenotypes and the compositional and functional profiles of the gut microbiota. Multivariate statistical tools, such as principal component analysis, redundancy analysis and partial least squares models, can be used to identify candidate key members of the gut microbiota as putative causative agents. Sequence-guided isolation should then be carried out to obtain a pure culture of the key bacteria, followed by reproduction of the disease in gnotobiotic animals associated with the key bacterium and/or a defined consortium of relevant bacteria, to generate a gnotobiotic model of the disease. For those diseases for which it is difficult to obtain a pure culture of the candidate key bacteria, large-scale interventional studies can be carried out to assess whether a reduction in the levels of candidate sequences leads to an improvement in the disease phenotypes. A multi-omics covariation analysis might be used to examine the correlating patterns of changes for the candidate key players and faecal, urinary, serum and/or plasma metabolites, or even whole transcriptomic or proteomic pathways; any such correlations might be indicative of a mechanistic connection between the putative cause and the disease.


  1. WHO. Obesity: Preventing and Managing the Global Epidemic. Report of a WHO consultation (WHO Technical Report Series 894) (WHO, 2000).
  2. Conterno, L., Fava, F., Viola, R. & Tuohy, K. M. Obesity and the gut microbiota: does up-regulating colonic fermentation protect against obesity and metabolic disease? Genes Nutr. 6, 241260 (2011).
  3. Sassi, F. Obesity and the Economics of Prevention: Fit not Fat (OECD Publishing, 2010).
  4. Popkin, B. M., Kim, S., Rusev, E. R., Du, S. & Zizza, C. Measuring the full economic costs of diet, physical activity and obesity-related chronic diseases. Obes. Rev. 7, 271293 (2006).
  5. Wang, Y., Beydoun, M. A., Liang, L., Caballero, B. & Kumanyika, S. K. Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring) 16, 23232330 (2008).
  6. WHO. Preventing chronic diseases: a vital investment: WHO global report. (WHO, 2005).
  7. Tchernof, A. & Despres, J. P. Pathophysiology of human visceral obesity: an update. Physiol. Rev. 93, 359404 (2013).
  8. Xia, Q. & Grant, S. F. The genetics of human obesity. Ann. NY Acad. Sci. 1281, 178190 (2013).
  9. Kahn, S. E., Hull, R. L. & Utzschneider, K. M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840846 (2006).
  10. Lederberg, J. Infectious history. Science 288, 287293 (2000).
  11. Yang, X., Xie, L., Li, Y. & Wei, C. More than 9,000,000 unique genes in human gut bacterial community: estimating gene numbers inside a human body. PLoS ONE 4, e6074 (2009).
  12. Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 5560 (2012).
  13. Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 5965 (2010).
  14. Martin, R. et al. Human milk is a source of lactic acid bacteria for the infant gut. J. Pediatr. 143, 754758 (2003).
  15. Gronlund, M. M. et al. Maternal breast-milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease. Clin. Exp. Allergy 37, 17641772 (2007).
  16. Gueimonde, M., Laitinen, K., Salminen, S. & Isolauri, E. Breast milk: a source of bifidobacteria for infant gut development and maturation? Neonatology 92, 6466 (2007).
  17. Martin, R. et al. Isolation of bifidobacteria from breast milk and assessment of the bifidobacterial population by PCR-denaturing gradient gel electrophoresis and quantitative real-time PCR. Appl. Environ. Microbiol. 75, 965969 (2009).
  18. Solis, G., de Los Reyes-Gavilan, C. G., Fernandez, N., Margolles, A. & Gueimonde, M. Establishment and development of lactic acid bacteria and bifidobacteria microbiota in breast-milk and the infant gut. Anaerobe 16, 307310 (2010).
  19. Collado, M. C., Isolauri, E., Laitinen, K. & Salminen, S. Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am. J. Clin. Nutr. 92, 10231030 (2010).
  20. Martin, R. et al. Early life: gut microbiota and immune development in infancy. Benef Microbes 1, 367382 (2010).
  21. Partty, A., Kalliomaki, M., Endo, A., Salminen, S. & Isolauri, E. Compositional development of Bifidobacterium and Lactobacillus microbiota is linked with crying and fussing in early infancy. PLoS ONE 7, e32495 (2012).
  22. Penders, J. et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 118, 511521 (2006).
  23. Rousseau, C. et al. Clostridium difficile colonization in early infancy is accompanied by changes in intestinal microbiota composition. J. Clin. Microbiol. 49, 858865 (2011).
  24. Zilber-Rosenberg, I. & Rosenberg, E. Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution. FEMS Microbiol. Rev. 32, 723735 (2008).
  25. Nicholson, J. K., Holmes, E. & Wilson, I. D. Gut microorganisms, mammalian metabolism and personalized health care. Nature Rev. Microbiol. 3, 431438 (2005).
  26. Carvalho, B. M. et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia 55, 28232834 (2012).
  27. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 16941697 (2009).
  28. Sonnenburg, J. L., Angenent, L. T. & Gordon, J. I. Getting a grip on things: how do communities of bacterial symbionts become established in our intestine? Nature Immunol. 5, 569573 (2004).
  29. Cummings, J. H. & Macfarlane, G. T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70, 443459 (1991).
  30. Englyst, H. N., Kingman, S. M., Hudson, G. J. & Cummings, J. H. Measurement of resistant starch in vitro and in vivo. Br. J. Nutr. 75, 749755 (1996).
  31. Miller, T. L., Weaver, G. A. & Wolin, M. J. Methanogens and anaerobes in a colon segment isolated from the normal fecal stream. Appl. Environ. Microbiol. 48, 449450 (1984).
  32. Soleim, H. A. & Scheline, R. R. Metabolism of xenobiotics by strains of intestinal bacteria. Acta Pharmacol. Toxicol. (Copenh.) 31, 471480 (1972).
  33. Macfarlane, G. T. & Macfarlane, S. Models for intestinal fermentation: association between food components, delivery systems, bioavailability and functional interactions in the gut. Curr. Opin. Biotechnol. 18, 156162 (2007).
  34. 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, 225235 (2013).
  35. Devkota, S. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature 487, 104108 (2012).
  36. Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 12681273 (2012).
  37. Konopka, A. Microbial ecology: searching for principles. Microbe 1, 175179 (2006).
  38. Zhang, C. et al. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 4, 232241 (2010).
  39. Zhang, C. et al. Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. ISME J. 6, 18481857 (2012).
  40. Parks, B. W. et al. Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice. Cell. Metab. 17, 141152 (2013).
  41. McFall-Ngai, M. Are biologists in 'future shock'? Symbiosis integrates biology across domains. Nature Rev. Microbiol. 6, 789792 (2008).
  42. Wikoff, W. R. et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl Acad. Sci. USA 106, 36983703 (2009).
  43. Hood, L. Tackling the microbiome. Science 336, 1209 (2012).
  44. Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 1673116736 (2008).
  45. Ozcan, U. et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313, 11371140 (2006).
  46. Rousseaux, C. et al. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nature Med. 13, 3537 (2007).
  47. Hill, M. J. Intestinal flora and endogenous vitamin synthesis. Eur. J. Cancer Prev. 6 (Suppl. 1), S43S45 (1997).
  48. McNeil, N. I. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 39, 338342 (1984).
  49. Hamer, H. M. et al. Review article: the role of butyrate on colonic function. Aliment. Pharmacol. Ther. 27, 104119 (2008).
  50. Lin, H. V. et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE 7, e35240 (2012).
  51. Archer, B. J., Johnson, S. K., Devereux, H. M. & Baxter, A. L. Effect of fat replacement by inulin or lupin-kernel fibre on sausage patty acceptability, post-meal perceptions of satiety and food intake in men. Br. J. Nutr. 91, 591599 (2004).
  52. Shen, J., Obin, M. S. & Zhao, L. The gut microbiota, obesity and insulin resistance. Mol. Aspects Med. 34, 3958 (2013).
  53. Sandler, R. H. et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J. Child Neurol. 15, 429435 (2000).
  54. Klinder, A., Forster, A., Caderni, G., Femia, A. P. & Pool-Zobel, B. L. Fecal water genotoxicity is predictive of tumor-preventive activities by inulin-like oligofructoses, probiotics (Lactobacillus rhamnosus and Bifidobacterium lactis), and their synbiotic combination. Nutr. Cancer 49, 144155 (2004).
  55. Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 17611772 (2007).
  56. Fei, N. & Zhao, L. An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice. ISME J. 7, 880884 (2013).
  57. Evans, A. S. Causation and disease: the Henle-Koch postulates revisited. Yale J. Biol. Med. 49, 175195 (1976).
  58. Pleasants, J. R. Rearing germfree cesarean-born rats, mice, and rabbits through weaning. Ann. NY Acad. Sci. 78, 116126 (1959).
  59. Suter, E. & Kirsanow, E. M. Fate of attenuated tubercle bacilli (BCG) in germ-free and conventional mice. Nature 195, 397398 (1962).
  60. Abrams, G. D., Bauer, H. & Sprinz, H. Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab. Invest. 12, 355364 (1963).
  61. Skelly, B. J., Trexler, P. C. & Tanami, J. Effect of a Clostridium species upon cecal size of gnotobiotic mice. Proc. Soc. Exp. Biol. Med. 100, 455458 (1962).
  62. Turnbaugh, P. J., Bäckhed, F., Fulton, L. & Gordon, J. I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213223 (2008).
  63. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 10271031 (2006).
  64. Bäckhed, F., Manchester, J. K., Semenkovich, C. F. & Gordon, J. I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl Acad. Sci. USA 104, 979984 (2007).
  65. Ding, S. et al. High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS ONE 5, e12191 (2010).
  66. Rabot, S. et al. Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J. 24, 49484959 (2010).
  67. Fleissner, C. K. et al. Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br. J. Nutr. 104, 919929 (2010).
  68. Zuo, F., Nakamura, N., Akao, T. & Hattori, M. Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ-free rats determined by liquid chromatography/ion trap mass spectrometry. Drug Metab. Dispos. 34, 20642072 (2006).
  69. Liu, H. et al. Metabolism and pharmacokinetics of mangiferin in conventional rats, pseudo-germ-free rats, and streptozotocin-induced diabetic rats. Drug Metab. Dispos. 40, 21092118 (2012).
  70. Cani, P. D. et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 14701481 (2008).
  71. Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328, 228231 (2010).
  72. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. & Medzhitov, R. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118, 229241 (2004).
  73. Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 5763 (2011).
  74. Clarke, T. B. et al. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nature Med. 16, 228231 (2010).
  75. Cho, I. et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488, 621626 (2012).
  76. Vrieze, A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913916 (2012).
  77. Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 1107011075 (2005).
  78. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 10221023 (2006).
  79. Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480484 (2009).
  80. Zhang, H. et al. Human gut microbiota in obesity and after gastric bypass. Proc. Natl Acad. Sci. USA 106, 23652370 (2009).
  81. Armougom, F., Henry, M., Vialettes, B., Raccah, D. & Raoult, D. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS ONE 4, e7125 (2009).
  82. Furet, J. P. et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes 59, 30493057 (2010).
  83. Mozes, S., Bujnakova, D., Sefcikova, Z. & Kmet, V. Developmental changes of gut microflora and enzyme activity in rat pups exposed to fat-rich diet. Obesity (Silver Spring) 16, 26102615 (2008).
  84. Santacruz, A. et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br. J. Nutr. 104, 8392 (2010).
  85. Waldram, A. et al. Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents. J. Proteome Res. 8, 23612375 (2009).
  86. Balamurugan, R. et al. Quantitative differences in intestinal Faecalibacterium prausnitzii in obese Indian children. Br. J. Nutr. 103, 335338 (2010).
  87. Collado, M. C., Isolauri, E., Laitinen, K. & Salminen, S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am. J. Clin. Nutr. 88, 894899 (2008).
  88. Duncan, S. H. et al. Human colonic microbiota associated with diet, obesity and weight loss. Int. J. Obes. (Lond.) 32, 17201724 (2008).
  89. Jumpertz, R. et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am. J. Clin. Nutr. 94, 5865 (2011).
  90. Schwiertz, A. et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18, 190195 (2010).
  91. Zupancic, M. L. et al. Analysis of the gut microbiota in the old order Amish and its relation to the metabolic syndrome. PLoS ONE 7, e43052 (2012).
  92. Murphy, E. F. et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59, 16351642 (2010).
  93. Zhang, X. et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS ONE 7, e42529 (2012).
  94. Neyrinck, A. M. et al. Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice. Nutr. Diabetes 2, e28 (2012).
  95. Beutler, B. & Rietschel, E. T. Innate immune sensing and its roots: the story of endotoxin. Nature Rev. Immunol. 3, 169176 (2003).
  96. Lindberg, A. A., Weintraub, A., Zahringer, U. & Rietschel, E. T. Structure-activity relationships in lipopolysaccharides of Bacteroides fragilis. Rev. Infect. Dis. 12 (Suppl. 2), S133S141 (1990).
  97. de La Serre, C. B. et al. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G440G448 (2010).
  98. Sotos, M. et al. Gut microbes and obesity in adolescents. Proc. Nutr. Soc. 67, E20 (2008).
  99. Amar, J. et al. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol. Med. 3, 559572 (2011).
  100. Amar, J. et al. Involvement of tissue bacteria in the onset of diabetes in humans: evidence for a concept. Diabetologia 54, 30553061 (2011).
  101. Schumann, R. R. et al. Structure and function of lipopolysaccharide binding protein. Science 249, 14291431 (1990).
  102. Weiss, J. Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP): structure, function and regulation in host defence against Gram-negative bacteria. Biochem. Soc. Trans. 31, 785790 (2003).
  103. Siebler, J., Galle, P. R. & Weber, M. M. The gut–liver-axis: endotoxemia, inflammation, insulin resistance and NASH. J. Hepatol 48, 10321034 (2008).
  104. Hotamisligil, G. S. et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance. Science 271, 665668 (1996).
  105. Ruiz, A. G. et al. Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obes. Surg. 17, 13741380 (2007).
  106. Wellen, K. E. & Hotamisligil, G. S. Inflammation, stress, and diabetes. J. Clin. Invest. 115, 11111119 (2005).
  107. Creely, S. J. et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 292, E740E747 (2007).
  108. Sun, L. et al. A marker of endotoxemia is associated with obesity and related metabolic disorders in apparently healthy Chinese. Diabetes Care 33, 19251932 (2010).
  109. Muccioli, G. G. et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 6, 392 (2010).
  110. Winter, S. E. et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339, 708711 (2013).
  111. Ghoshal, S., Witta, J., Zhong, J., de Villiers, W. & Eckhardt, E. Chylomicrons promote intestinal absorption of lipopolysaccharides. J. Lipid Res. 50, 9097 (2009).
  112. Bäckhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 1571815723 (2004).
  113. Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA (2013).
  114. Donnelly, P. Progress and challenges in genome-wide association studies in humans. Nature 456, 728731 (2008).
  115. Wang, T. et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 6, 320329 (2012).
  116. Nicholson, J. K. et al. Host-gut microbiota metabolic interactions. Science 336, 12621267 (2012).
  117. Li, M. et al. Symbiotic gut microbes modulate human metabolic phenotypes. Proc. Natl Acad. Sci. USA 105, 21172122 (2008).
  118. Caporaso, J. G. et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 6, 16211624 (2012).
  119. Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nature Methods 7, 335336 (2010).
  120. Hamady, M., Lozupone, C. & Knight, R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 4, 1727 (2010).
  121. Knights, D., Costello, E. K. & Knight, R. Supervised classification of human microbiota. FEMS Microbiol. Rev. 35, 343359 (2011).
  122. Sieber, J. R., McInerney, M. J. & Gunsalus, R. P. Genomic insights into syntrophy: the paradigm for anaerobic metabolic cooperation. Annu. Rev. Microbiol. 66, 429452 (2012).
  123. Samuel, B. S. & Gordon, J. I. A humanized gnotobiotic mouse model of host–archaeal–bacterial mutualism. Proc. Natl Acad. Sci. USA 103, 1001110016 (2006).
  124. DuPont, A. W. & DuPont, H. L. The intestinal microbiota and chronic disorders of the gut. Nature Rev. Gastroenterol. Hepatol 8, 523531 (2011).
  125. Chow, J., Tang, H. & Mazmanian, S. K. Pathobionts of the gastrointestinal microbiota and inflammatory disease. Curr. Opin. Immunol. 23, 473480 (2011).
  126. WHO. Obesity and overweight. Fact sheet no. 311. WHO Media Centre [online], (2012).
  127. Ogden, C. L. et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295, 15491555 (2006).
  128. Wang, Y., Mi, J., Shan, X. Y., Wang, Q. J. & Ge, K. Y. Is China facing an obesity epidemic and the consequences? The trends in obesity and chronic disease in China. Int. J. Obes. (Lond.) 31, 177188 (2007).
  129. Morrison, J. A., Friedman, L. A., Wang, P. & Glueck, C. J. Metabolic syndrome in childhood predicts adult metabolic syndrome and type 2 diabetes mellitus 25 to 30 years later. J. Pediatr. 152, 201206 (2008).
  130. Serdula, M. K. et al. Do obese children become obese adults? A review of the literature. Prev. Med. 22, 167177 (1993).
  131. Fredericks, D. N. & Relman, D. A. Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates. Clin. Microbiol. Rev. 9, 1833 (1996).
  132. Falkow, S. Molecular Koch's postulates applied to microbial pathogenicity. Rev. Infect. Dis. 10 (Suppl. 2), S274S276 (1988).
  133. Falkow, S. Molecular Koch's postulates applied to bacterial pathogenicity — a personal recollection 15 years later. Nature Rev. Microbiol. 2, 6772 (2004).

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  1. State Key Laboratory for Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University. Ministry of Education Key Laboratory for Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang Campus, Shanghai 200240, China.

    • Liping Zhao

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  • Liping Zhao

    Liping Zhao is currently a professor of microbiology and the Director of the Laboratory of Microbial Ecology and Ecogenomics, which is part of the State Key Laboratory for Microbial Metabolism in the School of Life Sciences and Biotechnology, Shanghai Jiao Tong University (SJTU), China. He is also the Director of the Laboratory of Nutritional Systems Biology, which is part of the Ministry of Education Key Laboratory for Systems Biomedicine in the Shanghai Center for Systems Biomedicine, SJTU, and Director of the SJTU-Perfect (China) Joint Research Center on Microbiota and Health. His research involves the application of molecular and genomic tools to gain a systems-level understanding of the complex microbial communities in the human and animal gut, and to be able to predictively manipulate these communities. His current focus is on the interactions between nutrition and the gut microbiota in the onset and progression of chronic diseases such as obesity and diabetes, and on how traditional Chinese medicine and medicinal foods might modulate this relationship to achieve preventive health care. Liping Zhao's homepage

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