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You are what you eat: diet, health and the gut microbiota

Abstract

Since the renaissance of microbiome research in the past decade, much insight has accumulated in comprehending forces shaping the architecture and functionality of resident microorganisms in the human gut. Of the multiple host-endogenous and host-exogenous factors involved, diet emerges as a pivotal determinant of gut microbiota community structure and function. By introducing dietary signals into the nexus between the host and its microbiota, nutrition sustains homeostasis or contributes to disease susceptibility. Herein, we summarize major concepts related to the effect of dietary constituents on the gut microbiota, highlighting chief principles in the diet–microbiota crosstalk. We then discuss the health benefits and detrimental consequences that the interactions between dietary and microbial factors elicit in the host. Finally, we present the promises and challenges that arise when seeking to incorporate microbiome data in dietary planning and portray the anticipated revolution that the field of nutrition is facing upon adopting these novel concepts.

Key points

  • Common multifactorial diseases in both industrialized and developing countries are often related to diet, yet current nutritional approaches aimed at their treatment and prevention are of limited efficacy.

  • Diet contents and quantity have a major role in shaping the human microbiota composition and function.

  • Complex interactions between nutrients and microorganisms dictate beneficial or detrimental outcomes to host health.

  • Conflicting reports highlight several nutrients, metabolites and microorganisms as both beneficial and detrimental to host health, which could stem from methodological differences between studies and interindividual variations.

  • Personalized nutrition is an emerging data-driven approach, potentially enabling diets tailored to the individual in various clinical contexts.

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Fig. 1: Temporal dietary modulation of the gut microbiota.
Fig. 2: Microbiota–diet interactions in the metabolic syndrome.
Fig. 3: Therapeutic principles in utilizing the food–microbiota axis.

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References

  1. Cho, I. & Blaser, M. J. The human microbiome: at the interface of health and disease. Nat. Rev. Genet. 13, 260–270 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sonnenburg, J. L. & Backhed, F. Diet-microbiota interactions as moderators of human metabolism. Nature 535, 56–64 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Collaboration, N. R. F. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387, 1377–1396 (2016).

    Article  Google Scholar 

  4. Ayyad, C. & Andersen, T. Long-term efficacy of dietary treatment of obesity: a systematic review of studies published between 1931 and 1999. Obes. Rev. 1, 113–119 (2000).

    Article  CAS  PubMed  Google Scholar 

  5. Tsai, A. G. & Wadden, T. A. Systematic review: an evaluation of major commercial weight loss programs in the United States. Ann. Internal Med. 142, 56–66 (2005).

    Article  Google Scholar 

  6. Gibson, P. & Shepherd, S. Personal view: food for thought–western lifestyle and susceptibility to Crohn’s disease. The FODMAP hypothesis. Aliment. Pharmacol. Ther. 21, 1399–1409 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Lee, J. et al. British Dietetic Association evidence-based guidelines for the dietary management of Crohn’s disease in adults. J. Hum. Nutr. Dietet. 27, 207–218 (2014).

    Article  CAS  Google Scholar 

  8. Marsh, A., Eslick, E. M. & Eslick, G. D. Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis. Eur. J. Nutr. 55, 897–906 (2016).

    Article  CAS  PubMed  Google Scholar 

  9. Manzel, A. et al. Role of “Western diet” in inflammatory autoimmune diseases. Curr. Allergy Asthma Rep. 14, 404 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fuchs, C. S. et al. Dietary fiber and the risk of colorectal cancer and adenoma in women. N. Engl. J. Med. 1999, 169–176 (1999).

    Article  Google Scholar 

  11. Bradbury, K. E., Appleby, P. N. & Key, T. J. Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Am. J. Clin. Nutr. 100, 394S–398S (2014).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Laursen, M. F., Bahl, M. I., Michaelsen, K. F. & Licht, T. R. First foods and gut microbes. Front. Microbiol. 8, 356 (2017).

    PubMed  PubMed Central  Google Scholar 

  14. Claesson, M. J. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 488, 178–184 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. Turnbaugh, P. J. et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci. Transl Med. 1, 6ra14 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Korem, T. et al. Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples. Science 349, 1101–1106 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cantarel, B. L., Lombard, V. & Henrissat, B. Complex carbohydrate utilization by the healthy human microbiome. PLOS One 7, e28742 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Eilam, O. et al. Glycan degradation (GlyDeR) analysis predicts mammalian gut microbiota abundance and host diet-specific adaptations. mBio 5, e01526–14 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sonnenburg, E. D. et al. Specificity of polysaccharide use in intestinal bacteroides species determines diet-induced microbiota alterations. Cell 141, 1241–1252 (2010). This work sheds light on a mechanism by which diet shapes the microbiota and proposes that genetic and structural analyses of Bacteroides species can infer their metabolic capacity and predict competitiveness in the presence of specific dietary polysaccharides.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Scott, K. P. et al. Substrate-driven gene expression in Roseburia inulinivorans: importance of inducible enzymes in the utilization of inulin and starch. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4672–4679 (2011).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hoek, M. & Merks, R. M. H. Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. BMC Syst. Biol. 11, 56 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Freilich, S. et al. Competitive and cooperative metabolic interactions in bacterial communities. Nat. Commun. 2, 589 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Cowan, M. M. Plant products as antimicrobial agents. Clin. Microbiol. Rev. 12, 564–582 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li, Y. et al. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147, 629–640 (2011). This work provides an example of an indirect mechanism for dietary modulation of the microbiota structure via the host immune system.

    Article  CAS  PubMed  Google Scholar 

  30. Hibberd, M. C. et al. The effects of micronutrient deficiencies on bacterial species from the human gut microbiota. Sci. Transl Med. 9, eaal4069 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Su, D. et al. Vitamin D signaling through induction of paneth cell defensins maintains gut microbiota and improves metabolic disorders and hepatic steatosis in animal models. Front. Physiol. 7, 498 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ooi, J. H., Li, Y., Rogers, C. J. & Cantorna, M. T. Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate-induced colitis. J. Nutr. 143, 1679–1686 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Luthold, R. V., Fernandes, G. R., Franco-de-Moraes, A. C., Folchetti, L. G. & Ferreira, S. R. Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals. Metabolism 69, 76–86 (2017).

    Article  CAS  PubMed  Google Scholar 

  34. Kaliannan, K., Wang, B., Li, X. Y., Kim, K. J. & Kang, J. X. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci. Rep. 5, 11276 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. He, B. et al. Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors. J. Exp. Med. 214, 107–123 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013). This work suggests a mechanism by which diet-derived bacterial metabolites regulate the host immune system and confer health-promoting effects.

    Article  CAS  PubMed  Google Scholar 

  37. Inagaki, T. et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl Acad. Sci. USA 103, 3920–3925 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chassaing, B. et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519, 92–96 (2015). This study presents an example of a food additive disrupting homeostasis in a microbiota-dependent manner, resulting in low-grade inflammation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kim, K.-A., Gu, W., Lee, I.-A., Joh, E.-H. & Kim, D.-H. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLOS One 7, e47713 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Schroeder, B. O. et al. Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell Host Microbe 23, 27–40 (2018).

    Article  CAS  PubMed  Google Scholar 

  41. Desai, M. S. et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 1339–1353 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zou, J. et al. Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host Microbe 23, 41–53 (2018).

    Article  CAS  PubMed  Google Scholar 

  43. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014). This work illustrates passive transfer of foodborne microorganisms into the gut indigenous microbial ecosystem and presents short-term structural and functional microbiota alterations typical of animal-based versus plant-based diets in humans.

    Article  CAS  PubMed  Google Scholar 

  44. Zhang, C. et al. Ecological robustness of the gut microbiota in response to ingestion of transient food-borne microbes. ISME J. 10, 2235–2245 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332, 970–974 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Schnorr, S. L. et al. Gut microbiome of the Hadza hunter-gatherers. Nat. Commun. 5, 3654 (2014).

    Article  CAS  PubMed  Google Scholar 

  50. Smits, S. A. et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania. Science 357, 802–806 (2017). This study demonstrates seasonality in the composition of faecal microbiota obtained from hunter-gatherers, which corresponds to the availability of different types of foods, and delineates the difference between this population and the industrialized population.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Obregon-Tito, A. J. et al. Subsistence strategies in traditional societies distinguish gut microbiomes. Nat. Commun. 6, 6505 (2015).

    Article  CAS  PubMed  Google Scholar 

  52. Martinez, I. et al. The gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes. Cell Rep. 11, 527–538 (2015).

    Article  CAS  PubMed  Google Scholar 

  53. Clemente, J. C. et al. The microbiome of uncontacted Amerindians. Sci. Adv. 1, e1500183 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cotillard, A. et al. Dietary intervention impact on gut microbial gene richness. Nature 500, 585–588 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. Hildebrandt, M. A. et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137, 1716–1724 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. 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, 213–223 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–1772 (2007).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Korem, T. et al. Bread affects clinical parameters and induces gut microbiome-associated personal glycemic responses. Cell Metab. 25, 1243–1253 (2017).

    Article  CAS  PubMed  Google Scholar 

  61. Shulman, R. J. et al. Psyllium fiber reduces abdominal pain in children with irritable bowel syndrome in a randomized, double-blind trial. Clin. Gastroenterol. Hepatol. 15, 712–719 (2017).

    Article  CAS  PubMed  Google Scholar 

  62. Fransen, F. et al. beta2-→1-Fructans modulate the immune system in vivo in a microbiota-dependent and -independent fashion. Front. Immunol. 8, 154 (2017).

    PubMed  PubMed Central  Google Scholar 

  63. Dimova, L. G., Zlatkov, N., Verkade, H. J., Uhlin, B. E. & Tietge, U. J. F. High-cholesterol diet does not alter gut microbiota composition in mice. Nutr. Metab. 14, 15 (2017).

    Article  CAS  Google Scholar 

  64. Smith, M. I. et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548–554 (2013). This work in children with undernutrition highlights the interrelationship between the microbiota and a nutrient-deficient diet.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Reyes, A. et al. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc. Natl Acad. Sci. USA 112, 11941–11946 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Subramanian, S. et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510, 417–421 (2014). This work devises a model to assess the ‘relative microbiota maturity index’ as a marker for malnutrition and the efficacy of therapeutic intervention.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L. & Gordon, J. I. Human nutrition, the gut microbiome and the immune system. Nature 474, 327–336 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zhang, C. et al. Structural modulation of gut microbiota in life-long calorie-restricted mice. Nat. Commun. 4, 2163 (2013).

    Article  CAS  PubMed  Google Scholar 

  69. Wu, J. et al. metabolomics insights into the modulatory effects of long-term low calorie intake in mice. J. Proteome Res. 15, 2299–2308 (2016).

    Article  CAS  PubMed  Google Scholar 

  70. Duncan, S. H. et al. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl. Environ. Microbiol. 73, 1073–1078 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Santacruz, A. et al. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obes. (Silver Spring, Md.) 17, 1906–1915 (2009).

    Article  Google Scholar 

  72. Ruiz, A. et al. One-year calorie restriction impacts gut microbial composition but not its metabolic performance in obese adolescents. Environ. Microbiol. 19, 1536–1551 (2017).

    Article  CAS  PubMed  Google Scholar 

  73. Fontana, L. & Partridge, L. Promoting health and longevity through diet: from model organisms to humans. Cell 161, 106–118 (2015). This review summarizes the interplay between dietary restriction, the gut microbiota and the host to explain lifespan extension and amelioration in ageing-associated diseases in various organisms.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Dao, M. C. et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65, 426–436 (2016).

    Article  CAS  PubMed  Google Scholar 

  75. Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (2013).

    Article  CAS  PubMed  Google Scholar 

  76. Thaiss, C. A. et al. Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature 540, 544–551 (2016). The study demonstrates ‘microbiome memory’ mediated by polyphenols that contributes to exacerbated weight gain in ‘yo-yo’ dieting.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  78. Thaiss, C. A. et al. Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167, 1495–1510. e1412 (2016).

    Article  CAS  PubMed  Google Scholar 

  79. Leone, V. et al. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe 17, 681–689 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Liang, X., Bushman, F. D. & FitzGerald, G. A. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proc. Natl Acad. Sci. USA 112, 10479–10484 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Zarrinpar, A., Chaix, A., Yooseph, S. & Panda, S. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab. 20, 1006–1017 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. David, L. A. et al. Host lifestyle affects human microbiota on daily timescales. Genome Biol. 15, R89 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ten Bruggencate, S. J., Bovee-Oudenhoven, I. M., Lettink-Wissink, M. L., Katan, M. B. & van der Meer, R. Dietary fructooligosaccharides affect intestinal barrier function in healthy men. J. Nutr. 136, 70–74 (2006).

    Article  PubMed  Google Scholar 

  84. Kovatcheva-Datchary, P. et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 22, 971–982 (2015). This work exemplifies that the presence of a specific gut microbiota composition in humans can dictate the host response to food.

    Article  CAS  PubMed  Google Scholar 

  85. Walker, A. W. et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 5, 220–230 (2011).

    Article  CAS  PubMed  Google Scholar 

  86. Lappi, J. et al. Intake of whole-grain and fiber-rich rye bread versus refined wheat bread does not differentiate intestinal microbiota composition in Finnish adults with metabolic syndrome. J. Nutr. 143, 648–655 (2013).

    Article  CAS  PubMed  Google Scholar 

  87. Jumpertz, R. et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am. J. Clin. Nutr. 94, 58–65 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Mariat, D. et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 9, 123 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Koenig, J. E. et al. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4578–4585 (2011).

    Article  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Thevaranjan, N. et al. Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe 21, 455–466 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Jeffery, I. B., Lynch, D. B. & O’Toole, P. W. Composition and temporal stability of the gut microbiota in older persons. ISME J. 10, 170–182 (2016).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Ma, J. et al. High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model. Nat. Commun. 5, 3889 (2014).

    Article  CAS  PubMed  Google Scholar 

  98. Myles, I. A. et al. Parental dietary fat intake alters offspring microbiome and immunity. J. Immunol. 191, 3200–3209 (2013).

    Article  CAS  PubMed  Google Scholar 

  99. Wankhade, U. D. et al. Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations. PLOS One 12, e0175675 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bibi, S., Kang, Y., Du, M. & Zhu, M. J. Maternal high-fat diet consumption enhances offspring susceptibility to DSS-induced colitis in mice. Obesity 25, 901–908 (2017).

    Article  CAS  PubMed  Google Scholar 

  101. Tompkins, G. R., O’Dell, N. L., Bryson, I. T. & Pennington, C. B. The effects of dietary ferric iron and iron deprivation on the bacterial composition of the mouse intestine. Curr. Microbiol. 43, 38–42 (2001).

    Article  CAS  PubMed  Google Scholar 

  102. Werner, T. et al. Depletion of luminal iron alters the gut microbiota and prevents Crohn’s disease-like ileitis. Gut 60, 325–333 (2011).

    Article  CAS  PubMed  Google Scholar 

  103. Dostal, A. et al. Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. J. Nutr. 142, 271–277 (2012).

    Article  CAS  PubMed  Google Scholar 

  104. Balamurugan, R. et al. Low levels of faecal lactobacilli in women with iron-deficiency anaemia in south India. Br. J. Nutr. 104, 931–934 (2010).

    Article  CAS  PubMed  Google Scholar 

  105. Pachikian, B. D. et al. Changes in intestinal bifidobacteria levels are associated with the inflammatory response in magnesium-deficient mice. J. Nutr. 140, 509–514 (2010).

    Article  CAS  PubMed  Google Scholar 

  106. Starke, I. C., Pieper, R., Neumann, K., Zentek, J. & Vahjen, W. The impact of high dietary zinc oxide on the development of the intestinal microbiota in weaned piglets. FEMS Microbiol. Ecol. 87, 416–427 (2014).

    Article  CAS  PubMed  Google Scholar 

  107. Mayneris-Perxachs, J. et al. Protein- and zinc-deficient diets modulate the murine microbiome and metabolic phenotype. Am. J. Clin. Nutr. 104, 1253–1262 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Speckmann, B. & Steinbrenner, H. Selenium and selenoproteins in inflammatory bowel diseases and experimental colitis. Inflamm. Bowel Dis. 20, 1110–1119 (2014).

    PubMed  Google Scholar 

  109. Kina-Tanada, M. et al. Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice. Diabetologia 60, 1138–1151 (2017).

    Article  CAS  PubMed  Google Scholar 

  110. Assa, A. et al. Vitamin D deficiency promotes epithelial barrier dysfunction and intestinal inflammation. J. Infect. Dis. 210, 1296–1305 (2014).

    Article  CAS  PubMed  Google Scholar 

  111. Etxeberria, U. et al. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J. Nutr. Biochem. 26, 651–660 (2015).

    Article  CAS  PubMed  Google Scholar 

  112. Huang, J. et al. Different flavonoids can shape unique gut microbiota profile in vitro. J. Food Sci. 81, H2273–H2279 (2016).

    Article  CAS  PubMed  Google Scholar 

  113. Anhê, F. F. et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut 64, 872–883 (2015).

    Article  CAS  PubMed  Google Scholar 

  114. Wu, G. D. et al. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut 65, 63–72 (2016).

    Article  CAS  PubMed  Google Scholar 

  115. O’Keefe, S. J. et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat. Commun. 6, 6342 (2015).

    Article  CAS  PubMed  Google Scholar 

  116. McDonald, D. et al. American Gut: an open platform for citizen science microbiome research. mSystems 3, e00031–18 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Sazawal, S. et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 367, 133–143 (2006).

    Article  CAS  PubMed  Google Scholar 

  118. Jaeggi, T. et al. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut 64, 731–742 (2014).

    Article  CAS  PubMed  Google Scholar 

  119. Tung, J. et al. Social networks predict gut microbiome composition in wild baboons. eLife 4, e05224 (2015).

    Article  PubMed Central  Google Scholar 

  120. Song, S. J. et al. Cohabiting family members share microbiota with one another and with their dogs. eLife 2, e00458 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Griffin, N. W. et al. Prior dietary practices and connections to a human gut microbial metacommunity alter responses to diet interventions. Cell Host Microbe 21, 84–96 (2017).

    Article  CAS  PubMed  Google Scholar 

  122. Brito, I. L. et al. Mobile genes in the human microbiome are structured from global to individual scales. Nature 535, 435–439 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Thomas, F., Hehemann, J. H., Rebuffet, E., Czjzek, M. & Michel, G. Environmental and gut bacteroidetes: the food connection. Front. Microbiol. 2, 93 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Hehemann, J.-H. et al. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464, 908–912 (2010).

    Article  CAS  PubMed  Google Scholar 

  125. Shepherd, E. S., DeLoache, W. C., Pruss, K. M., Whitaker, W. R. & Sonnenburg, J. L. An exclusive metabolic niche enables strain engraftment in the gut microbiota. Nature 557, 434–438 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Perry, G. H. et al. Diet and the evolution of human amylase gene copy number variation. Nat. Genet. 39, 1256–1260 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Johnson, J. S. et al. 11beta-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet. J. Endocrinol. 232, 273–283 (2017).

    Article  CAS  PubMed  Google Scholar 

  128. Ruan, J. W. et al. Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice. Nat. Microbiol. 2, 16220 (2016).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ussar, S. et al. Interactions between gut microbiota, host genetics and diet modulate the predisposition to obesity and metabolic syndrome. Cell Metab. 22, 516–530 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Rothschild, D. et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 555, 210–215 (2018).

    Article  CAS  PubMed  Google Scholar 

  132. Koh, A., De Vadder, F., Kovatcheva-Datchary, P. & Backhed, F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165, 1332–1345 (2016). This work provides two mechanisms for SCFAs to activate intestinal gluconeogenesis either directly or through a gut–brain neural circuit.

    Article  CAS  PubMed  Google Scholar 

  133. Byndloss, M. X. et al. Microbiota-activated PPAR-gamma signaling inhibits dysbiotic Enterobacteriaceae expansion. Science 357, 570–575 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Gao, Z. et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 1509–1517 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Chambers, E. S. et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut 64, 1744–1754 (2015).

    Article  CAS  PubMed  Google Scholar 

  137. Venter, C. S., Vorster, H. H. & Cummings, J. H. Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers. Am. J. Gastroenterol. 85, 549–553 (1990).

    CAS  PubMed  Google Scholar 

  138. Canfora, E. E. et al. Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial. Sci. Rep. 7, 2360 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. De Vadder, F. et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84–96 (2014).

    Article  CAS  PubMed  Google Scholar 

  140. Frost, G. et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 5, 3611 (2014).

    Article  CAS  PubMed  Google Scholar 

  141. Maslowski, K. M. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282–1286 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Singh, N. et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40, 128–139 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Macia, L. et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6 (2015).

  144. Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T cell generation. Nature 504, 451–455 (2013). This work demonstrates how SCFAs, which are generated by the microbiota from non-digestible carbohydrates, take part in host immunomodulation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).

    Article  CAS  PubMed  Google Scholar 

  146. Thorburn, A. N. et al. Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. Nat. Commun. 6, 7320 (2015).

    Article  CAS  PubMed  Google Scholar 

  147. Trompette, A. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20, 159–166 (2014).

    Article  CAS  PubMed  Google Scholar 

  148. Hryckowian, A. J. et al. Microbiota-accessible carbohydrates suppress Clostridium difficile infection in a murine model. Nat. Microbiol. 3, 662–669 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Correa-Matos, N. J. et al. Fermentable fiber reduces recovery time and improves intestinal function in piglets following Salmonella typhimurium infection. J. Nutr. 133, 1845–1852 (2003).

    Article  CAS  PubMed  Google Scholar 

  150. McIntyre, A., Gibson, P. & Young, G. Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 34, 386–391 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Belcheva, A. et al. Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells. Cell 158, 288–299 (2014).

    Article  CAS  PubMed  Google Scholar 

  152. Siri-Tarino, P. W., Sun, Q., Hu, F. B. & Krauss, R. M. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am. J. Clin. Nutr. 91, 535–546 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Mozaffarian, D. & Ludwig, D. S. The 2015 US Dietary Guidelines: lifting the ban on total dietary fat. JAMA 313, 2421–2422 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Amar, J. et al. Energy intake is associated with endotoxemia in apparently healthy men. Am. J. Clin. Nutr. 87, 1219–1223 (2008).

    Article  CAS  PubMed  Google Scholar 

  155. Saberi, M. et al. Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. Cell Metab. 10, 419–429 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. 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, 1470–1481 (2008). This work shows for the first time that gut microbiota alterations can modulate HFD-induced metabolic endotoxaemia and its deleterious effects on the host.

    Article  CAS  PubMed  Google Scholar 

  157. Caesar, R., Tremaroli, V., Kovatcheva-Datchary, P., Cani, P. D. & Backhed, F. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 22, 658–668 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Fava, F. et al. The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’ population. Int. J. Obes. 37, 216–223 (2013).

    Article  CAS  Google Scholar 

  159. Cheng, L. et al. High fat diet exacerbates dextran sulfate sodium induced colitis through disturbing mucosal dendritic cell homeostasis. Int. Immunopharmacol. 40, 1–10 (2016).

    Article  CAS  PubMed  Google Scholar 

  160. Klebanoff, C. A. et al. Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. J. Exp. Med. 210, 1961–1976 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Devkota, S. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature 487, 104–108 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1131 (2006). This landmark study suggested for the first time that the microbiota of obese mice fed an HFD can harvest more energy from food; thus, this trait can be transmissible to other mice by microbiota transplantation.

    Article  PubMed  Google Scholar 

  163. Schwiertz, A. et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18, 190–195 (2010).

    Article  PubMed  Google Scholar 

  164. Murphy, E. et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59, 1635–1642 (2010).

    Article  CAS  PubMed  Google Scholar 

  165. Du, H. et al. Dietary fiber and subsequent changes in body weight and waist circumference in European men and women. Am. J. Clin. Nutr. 91, 329–336 (2009).

    Article  CAS  PubMed  Google Scholar 

  166. den Besten, G. et al. Short-chain fatty acids protect against high-fat diet–induced obesity via a PPARγ-dependent switch from lipogenesis to fat oxidation. Diabetes 64, 2398–2408 (2015).

    Article  CAS  Google Scholar 

  167. Perry, R. J. et al. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature 534, 213–217 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Haghikia, A. et al. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity 43, 817–829 (2015).

    Article  CAS  PubMed  Google Scholar 

  169. Lukens, J. R. et al. Dietary modulation of the microbiome affects autoinflammatory disease. Nature 516, 246–249 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Koeth, R. A. et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19, 576–585 (2013). This work presents a causative link between red meat consumption, its microbiota-derived metabolites and host-derived formation of atherogenic end products.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Zhu, W. et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 165, 111–124 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Butler, L. M. et al. Heterocyclic amines, meat intake, and association with colon cancer in a population-based study. Am. J. Epidemiol. 157, 434–445 (2003).

    Article  CAS  PubMed  Google Scholar 

  173. Bouvard, V. et al. Carcinogenicity of consumption of red and processed meat. Lancet Oncol. 16, 1599–1600 (2015).

    Article  PubMed  Google Scholar 

  174. Zsivkovits, M. et al. Prevention of heterocyclic amine-induced DNA damage in colon and liver of rats by different lactobacillus strains. Carcinogenesis 24, 1913–1918 (2003).

    Article  CAS  PubMed  Google Scholar 

  175. Ijssennagger, N. et al. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon. Proc. Natl Acad. Sci. USA 112, 10038–10043 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Hullar, M. A., Burnett-Hartman, A. N. & Lampe, J. W. Gut microbes, diet, and cancer. Cancer Treatment Res. 159, 377–399 (2014).

    Article  CAS  Google Scholar 

  177. Massey, R., Key, P., Mallett, A. & Rowland, I. An investigation of the endogenous formation of apparent total N-nitroso compounds in conventional microflora and germ-free rats. Food Chem. Toxicol. 26, 595–600 (1988).

    Article  CAS  PubMed  Google Scholar 

  178. FDA. Food additives and ingredients. Food and Drug Agency https://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/default.htm (2018).

  179. Chassaing, B., Van de Wiele, T., De Bodt, J., Marzorati, M. & Gewirtz, A. T. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut 66, 1414–1427 (2017).

    Article  CAS  PubMed  Google Scholar 

  180. Tang, W. W. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Suez, J., Korem, T., Zilberman-Schapira, G., Segal, E. & Elinav, E. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes 6, 149–155 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Suez, J. et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181–186 (2014).

    Article  CAS  PubMed  Google Scholar 

  183. Bian, X. et al. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem. Toxicol. 107, 530–539 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Labrecque, M. T., Malone, D., Caldwell, K. E. & Allan, A. M. Impact of ethanol and saccharin on fecal microbiome in pregnant and non-pregnant mice. J. Pregnancy Child Health 2, 193 (2015).

    Article  Google Scholar 

  185. Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E. & Schiffman, S. S. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J. Toxicol. Environ. Health, Part A 71, 1415–1429 (2008).

    Article  CAS  Google Scholar 

  186. Uebanso, T. et al. Effects of low-dose non-caloric sweetener consumption on gut microbiota in mice. Nutrients 9, 560 (2017).

    Article  CAS  PubMed Central  Google Scholar 

  187. Palmnäs, M. S. A. et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLOS One 9, e109841 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Gul, S. S. et al. Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice. Appl. Physiol., Nutr., Metab. 42, 77–83 (2016).

    Article  CAS  Google Scholar 

  189. Drasar, B., Renwick, A. & Williams, R. The role of the gut flora in the metabolism of cyclamate. Biochem. J. 129, 881–890 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Chi, L. et al. Effects of the artificial sweetener neotame on the gut microbiome and fecal metabolites in mice. Molecules (Basel, Switzerland) 23, 367 (2018).

    Article  CAS  Google Scholar 

  191. Bian, X. et al. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLOS One 12, e0178426 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Fischbach, M. A., Lin, H., Liu, D. R. & Walsh, C. T. How pathogenic bacteria evade mammalian sabotage in the battle for iron. Nat. Chem. Biol. 2, 132–138 (2006).

    Article  CAS  PubMed  Google Scholar 

  193. Juttukonda, L. J. et al. Dietary manganese promotes staphylococcal infection of the heart. Cell Host Microbe 22, 531–542 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Roopchand, D. E. et al. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet–induced metabolic syndrome. Diabetes 64, 2847–2858 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Cassidy, A. & Minihane, A.-M. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am. J. Clin. Nutr. 105, 10–22 (2017).

    Article  CAS  PubMed  Google Scholar 

  196. Laparra, J. M. & Sanz, Y. Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol. Res. 61, 219–225 (2010).

    Article  CAS  PubMed  Google Scholar 

  197. Couteau, D., McCartney, A., Gibson, G., Williamson, G. & Faulds, C. Isolation and characterization of human colonic bacteria able to hydrolyse chlorogenic acid. J. Appl. Microbiol. 90, 873–881 (2001).

    Article  CAS  PubMed  Google Scholar 

  198. Stewart, C. S., Duncan, S. H. & Cave, D. R. Oxalobacter formigenes and its role in oxalate metabolism in the human gut. FEMS Microbiol. Lett. 230, 1–7 (2004).

    Article  CAS  PubMed  Google Scholar 

  199. Chen, J. P., Chen, G. C., Wang, X. P., Qin, L. & Bai, Y. Dietary fiber and metabolic syndrome: a meta-analysis and review of related mechanisms. Nutrients 10, 24 (2018).

    Article  CAS  Google Scholar 

  200. Elinav, E. et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145, 745–757 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Lucke, K., Miehlke, S., Jacobs, E. & Schuppler, M. Prevalence of Bacteroides & Prevotella spp. in ulcerative colitis. J. Med. Microbiol. 55, 617–624 (2006).

    Article  CAS  PubMed  Google Scholar 

  202. Scher, J. U. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2, e01202 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Plovier, H. et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 23, 107–113 (2017).

    Article  CAS  PubMed  Google Scholar 

  205. Seregin, S. S. et al. NLRP6 protects Il10−/− mice from colitis by limiting colonization of Akkermansia muciniphila. Cell Rep. 19, 733–745 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

    Article  CAS  PubMed  Google Scholar 

  207. Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Verdam, F. J. et al. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity 21, E607–E615 (2013).

    Article  CAS  PubMed  Google Scholar 

  209. Duncan, S. H. et al. Human colonic microbiota associated with diet, obesity and weight loss. Int. J. Obes. 32, 1720–1724 (2008).

    Article  CAS  Google Scholar 

  210. Patil, D. P. et al. Molecular analysis of gut microbiota in obesity among Indian individuals. J. Biosci. 37, 647–657 (2012).

    Article  CAS  PubMed  Google Scholar 

  211. Tims, S. et al. Microbiota conservation and BMI signatures in adult monozygotic twins. ISME J. 7, 707 (2013).

    Article  CAS  PubMed  Google Scholar 

  212. Butzner, J., Parmar, R., Bell, C. & Dalal, V. Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat. Gut 38, 568–573 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Kreznar, J. H. et al. Host genotype and gut microbiome modulate insulin secretion and diet-induced metabolic phenotypes. Cell Rep. 18, 1739–1750 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Gibson, G. R. & Roberfroid, M. B. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J. Nutr. 125, 1401–1412 (1995).

    Article  CAS  PubMed  Google Scholar 

  215. Meyer, D. & Stasse-Wolthuis, M. The bifidogenic effect of inulin and oligofructose and its consequences for gut health. Eur. J. Clin. Nutr. 63, 1277 (2009).

    Article  CAS  PubMed  Google Scholar 

  216. Heilpern, D. & Szilagyi, A. Manipulation of intestinal microbial flora for therapeutic benefit in inflammatory bowel diseases: review of clinical trials of probiotics, prebiotics and synbiotics. Rev. Recent Clin. Trials 3, 167–184 (2008).

    Article  CAS  PubMed  Google Scholar 

  217. Arslanoglu, S. et al. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. J. Nutr. 138, 1091–1095 (2008).

    Article  CAS  PubMed  Google Scholar 

  218. Vulevic, J., Juric, A., Tzortzis, G. & Gibson, G. R. A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults. J. Nutr. 143, 324–331 (2013).

    Article  CAS  PubMed  Google Scholar 

  219. Arslanoglu, S., Moro, G. E. & Boehm, G. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. J. Nutr. 137, 2420–2424 (2007).

    Article  CAS  PubMed  Google Scholar 

  220. Cummings, J., Christie, S. & Cole, T. A study of fructo oligosaccharides in the prevention of travellers’ diarrhoea. Aliment. Pharmacol. Ther. 15, 1139–1145 (2001).

    Article  CAS  PubMed  Google Scholar 

  221. Davis, L. M., Martínez, I., Walter, J., Goin, C. & Hutkins, R. W. Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans. PLOS One 6, e25200 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Kolida, S., Meyer, D. & Gibson, G. A double-blind placebo-controlled study to establish the bifidogenic dose of inulin in healthy humans. Eur. J. Clin. Nutr. 61, 1189 (2007).

    Article  CAS  PubMed  Google Scholar 

  223. De Preter, V. et al. Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects. Aliment. Pharmacol. Ther. 27, 504–513 (2008).

    Article  CAS  PubMed  Google Scholar 

  224. Langlands, S., Hopkins, M., Coleman, N. & Cummings, J. Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut 53, 1610–1616 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Martínez, I. et al. Gut microbiome composition is linked to whole grain-induced immunological improvements. ISME J. 7, 269 (2013).

    Article  CAS  PubMed  Google Scholar 

  226. Henning, S. M. et al. Health benefit of vegetable/fruit juice-based diet: role of microbiome. Sci. Rep. 7, 2167 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Moran-Ramos, S. et al. Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats. PLOS One 12, e0171672 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Everard, A. et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60, 2775–2786 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Cani, P. D. et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50, 2374–2383 (2007).

    Article  CAS  PubMed  Google Scholar 

  230. Serino, M. et al. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 61, 543–553 (2012).

    Article  CAS  PubMed  Google Scholar 

  231. Chaplin, A., Parra, P., Serra, F. & Palou, A. Conjugated linoleic acid supplementation under a high-fat diet modulates stomach protein expression and intestinal microbiota in adult mice. PLOS One 10, e0125091 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Norris, G. H., Jiang, C., Ryan, J., Porter, C. M. & Blesso, C. N. Milk sphingomyelin improves lipid metabolism and alters gut microbiota in high fat diet-fed mice. J. Nutr. Biochem. 30, 93–101 (2016).

    Article  CAS  PubMed  Google Scholar 

  233. Shin, N.-R. et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63, 727–735 (2014).

    Article  CAS  PubMed  Google Scholar 

  234. de la Cuesta-Zuluaga, J. et al. Metformin is associated with higher relative abundance of mucin-degrading Akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care 40, 54–62 (2017).

    Article  CAS  PubMed  Google Scholar 

  235. Gibson, G. R. et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14, 491–502 (2017).

    PubMed  Google Scholar 

  236. Chen, M. et al. Dairy consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis. BMC Med. 12, 215 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  238. D’souza, A. L., Rajkumar, C., Cooke, J. & Bulpitt, C. J. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 324, 1361 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  239. Bibiloni, R. et al. VSL# 3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am. J. Gastroenterol. 100, 1539 (2005).

    Article  PubMed  Google Scholar 

  240. Allen, S. J. et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 382, 1249–1257 (2013).

    Article  PubMed  Google Scholar 

  241. Azad, M. B. et al. Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis. BMJ 347, f6471 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  242. Marteau, P. et al. Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn’s disease: a randomised, double blind, placebo controlled GETAID trial. Gut 55, 842–847 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. NCCIH. Probiotics: in depth. National Center for Complementary and Integrative Health https://nccih.nih.gov/health/probiotics/introduction.htm (2016).

  244. Hammerman, C., Bin-Nun, A. & Kaplan, M. Safety of probiotics: comparison of two popular strains. BMJ 333, 1006 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  245. Liu, R. et al. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat. Med. 23, 859 (2017).

    Article  CAS  PubMed  Google Scholar 

  246. Canani, R. B. et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ 335, 340 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  247. Mobini, R. et al. Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: a randomized controlled trial. Diabetes, Obes. Metab. 19, 579–589 (2017).

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Spencer, M. D. et al. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology 140, 976–986 (2011).

    Article  CAS  PubMed  Google Scholar 

  250. Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015). This paper highlights interindividual differences among humans, including microbiota composition and function, as drivers of variability in postprandial glycaemic responses to food items and suggests that diets should be tailor-made in order to better control blood glucose levels.

    Article  CAS  PubMed  Google Scholar 

  251. Pasquale, T. R. & Tan, J. S. Nonantimicrobial effects of antibacterial agents. Clin. Infect. Dis. 40, 127–135 (2005).

    Article  CAS  PubMed  Google Scholar 

  252. McDonald, J. A. et al. Simulating distal gut mucosal and luminal communities using packed-column biofilm reactors and an in vitro chemostat model. J. Microbiol. Methods 108, 36–44 (2015).

    Article  CAS  PubMed  Google Scholar 

  253. Lukovac, S. et al. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. mBio 5, e01438–14 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Yissachar, N. et al. An intestinal organ culture system uncovers a role for the nervous system in microbe-immune crosstalk. Cell 168, 1135–1148 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Warden, C. H. & Fisler, J. S. Comparisons of diets used in animal models of high-fat feeding. Cell Metab. 7, 277 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Adam, C. L. et al. Effects of dietary fibre (pectin) and/or increased protein (casein or pea) on satiety, body weight, adiposity and caecal fermentation in high fat diet-induced obese rats. PLOS One 11, e0155871 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Nguyen, T. L. A., Vieira-Silva, S., Liston, A. & Raes, J. How informative is the mouse for human gut microbiota research? Dis. Models Mechanisms 8, 1–16 (2015).

    Article  CAS  Google Scholar 

  258. Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013). This pioneering work shows that gut microbiota transfer from human twin pairs discordant for obesity is able to transmit the metabolic phenotype into GF mice and that this phenotype can be attributed to certain members of the microbiota.

    Article  CAS  PubMed  Google Scholar 

  259. Hildebrand, F. et al. Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice. Genome Biol. 14, R4 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  260. Al-Asmakh, M. & Zadjali, F. Use of germ-free animal models in microbiota-related research. J. Microbiol. Biotechnol. 25, 1583–1588 (2015).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Choo, J. M., Leong, L. E. & Rogers, G. B. Sample storage conditions significantly influence faecal microbiome profiles. Sci. Rep. 5, 16350 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Costea, P. I. et al. Towards standards for human fecal sample processing in metagenomic studies. Nat. Biotechnol. 35, 1069 (2017).

    CAS  PubMed  Google Scholar 

  264. Shah, N., Tang, H., Doak, T. G. & Ye, Y. in Biocomputing 2011, 165–176 (World Scientific, 2011).

  265. Claesson, M. J. et al. Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions. Nucleic Acids Res. 38, e200 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  266. Gohl, D. M. et al. Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies. Nat. Biotechnol. 34, 942 (2016).

    Article  CAS  PubMed  Google Scholar 

  267. de la Cuesta-Zuluaga, J. & Escobar, J. S. Considerations for optimizing microbiome analysis using a marker gene. Front. Nutr. 3, 26 (2016).

    PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Mandal, S. et al. Analysis of composition of microbiomes: a novel method for studying microbial composition. Microb. Ecol. Health Dis. 26, 27663 (2015).

    PubMed  Google Scholar 

  270. Vandeputte, D. et al. Quantitative microbiome profiling links gut community variation to microbial load. Nature 551, 507–511 (2017).

    Article  CAS  PubMed  Google Scholar 

  271. Kumar, S., Indugu, N., Vecchiarelli, B. & Pitta, D. W. Associative patterns among anaerobic fungi, methanogenic archaea, and bacterial communities in response to changes in diet and age in the rumen of dairy cows. Front. Microbiol. 6, 781 (2015).

    PubMed  PubMed Central  Google Scholar 

  272. Salgado-Flores, A. et al. Rumen and cecum microbiomes in reindeer (Rangifer tarandus tarandus) are changed in response to a lichen diet and may affect enteric methane emissions. PLOS One 11, e0155213 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  273. Hoffmann, C. et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLOS One 8, e66019 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Cuskin, F. et al. Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism. Nature 517, 165 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  275. Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  276. Minot, S. et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 21, 1616–1625 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. Kim, M. S. & Bae, J. W. Spatial disturbances in altered mucosal and luminal gut viromes of diet-induced obese mice. Environ. Microbiol. 18, 1498–1510 (2016).

    Article  CAS  PubMed  Google Scholar 

  278. Beck, M. A., Shi, Q., Morris, V. C. & Levander, O. A. Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nat. Med. 1, 433–436 (1995).

    Article  CAS  PubMed  Google Scholar 

  279. Willner, D. et al. Metagenomic detection of phage-encoded platelet-binding factors in the human oral cavity. Proc. Natl Acad. Sci. USA 108, 4547–4553 (2011).

    Article  CAS  PubMed  Google Scholar 

  280. Wang, X. et al. Cryptic prophages help bacteria cope with adverse environments. Nat. Commun. 1, 147 (2010).

    Article  CAS  PubMed  Google Scholar 

  281. Freitas, C. E. S. et al. Sheep fed with banana leaf hay reduce ruminal protozoa population. Trop. Animal Health Prod. 49, 807–812 (2017).

    Article  Google Scholar 

  282. Yang, W. et al. Effect of Bidens pilosa on infection and drug resistance of Eimeria in chickens. Res. Veterinary Sci. 98, 74–81 (2015).

    Article  CAS  Google Scholar 

  283. Ferguson, A., Logan, R. & MacDonald, T. Increased mucosal damage during parasite infection in mice fed an elemental diet. Gut 21, 37–43 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  284. Coop, R. & Holmes, P. Nutrition and parasite interaction. Int. J. Parasitol. 26, 951–962 (1996).

    Article  CAS  PubMed  Google Scholar 

  285. Williams, A. R. et al. Dietary cinnamaldehyde enhances acquisition of specific antibodies following helminth infection in pigs. Veterinary Immunol. Immunopathol. 189, 43–52 (2017).

    Article  CAS  Google Scholar 

  286. Morton, E. R. et al. Variation in rural African gut microbiota is strongly correlated with colonization by Entamoeba and subsistence. PLoS Genet. 11, e1005658 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  287. Nourrisson, C. et al. Blastocystis is associated with decrease of fecal microbiota protective bacteria: comparative analysis between patients with irritable bowel syndrome and control subjects. PLOS One 9, e111868 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  288. Wang, Y. et al. Metabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification. Proc. Natl Acad. Sci. USA 101, 12676–12681 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  289. Kay, G. L. et al. Differences in the faecal microbiome in Schistosoma haematobium infected children versus uninfected children. PLoS Negl. Trop. Diseases 9, e0003861 (2015).

    Article  CAS  Google Scholar 

  290. Mansfield, L. & Urban, Jr, J. The pathogenesis of necrotic proliferative colitis in swine is linked to whipworm induced suppression of mucosal immunity to resident bacteria. Veterinary Immunol. Immunopathol. 50, 1–17 (1996).

    Article  CAS  Google Scholar 

  291. Cantacessi, C. et al. Impact of experimental hookworm infection on the human gut microbiota. J. Infecti. Diseases 210, 1431–1434 (2014).

    Article  CAS  Google Scholar 

  292. Cooper, P. et al. Patent human infections with the whipworm, Trichuris trichiura, are not associated with alterations in the faecal microbiota. PLOS One 8, e76573 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  293. Plieskatt, J. L. et al. Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome. FASEB J. 27, 4572–4584 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  294. Yooseph, S. et al. Stool microbiota composition is associated with the prospective risk of Plasmodium falciparum infection. BMC Genom. 16, 631 (2015).

    Article  CAS  Google Scholar 

  295. Yilmaz, B. et al. Gut microbiota elicits a protective immune response against malaria transmission. Cell 159, 1277–1289 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  296. Villarino, N. F. et al. Composition of the gut microbiota modulates the severity of malaria. Proc. Natl Acad. Sci. USA 113, 2235–2240 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  297. Shukla, G., Bhatia, R. & Sharma, A. Prebiotic inulin supplementation modulates the immune response and restores gut morphology in Giardia duodenalis-infected malnourished mice. Parasitol. Res. 115, 4189–4198 (2016).

    Article  PubMed  Google Scholar 

  298. Newbold, L. K. et al. Helminth burden and ecological factors associated with alterations in wild host gastrointestinal microbiota. ISME J. 11, 663 (2017).

    Article  PubMed  Google Scholar 

  299. Houlden, A. et al. Chronic Trichuris muris infection in C57BL/6 mice causes significant changes in host microbiota and metabolome: effects reversed by pathogen clearance. PLOS One 10, e0125945 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  300. Li, R. W. et al. The effect of helminth infection on the microbial composition and structure of the caprine abomasal microbiome. Sci. Rep. 6, 20606 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  301. Wu, S. et al. Worm burden-dependent disruption of the porcine colon microbiota by Trichuris suis infection. PLOS One 7, e35470 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  302. Rutter, J. & Beer, R. Synergism between Trichuris suis and the microbial flora of the large intestine causing dysentery in pigs. Infection Immun. 11, 395–404 (1975).

    CAS  Google Scholar 

  303. Zaiss, M. M. et al. The intestinal microbiota contributes to the ability of helminths to modulate allergic inflammation. Immunity 43, 998–1010 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  304. Chen, Y. et al. Association of previous schistosome infection with diabetes and metabolic syndrome: a cross-sectional study in rural China. J. Clin. Endocrinol. Metab. 98, E283–E287 (2013).

    Article  CAS  PubMed  Google Scholar 

  305. Aravindhan, V. et al. Decreased prevalence of lymphatic filariasis among diabetic subjects associated with a diminished pro-inflammatory cytokine response (CURES 83). PLoS Negl. Trop. Diseases 4, e707 (2010).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the members of the Elinav laboratory for discussions and apologize to authors whose work was not cited because of space constraints. N.Z. is supported by the Gilead Sciences International Research Scholars Program in Liver Disease. J.S. is the recipient of the Strauss Institute Research Fellowship. E.E. is supported by Y. and R. Ungar, the Abisch Frenkel Foundation for the Promotion of Life Sciences, the Gurwin Family Fund for Scientific Research, the Leona M. and Harry B. Helmsley Charitable Trust, the Crown Endowment Fund for Immunological Research, the estate of J. Gitlitz, the estate of L. Hershkovich, the Benoziyo Endowment Fund for the Advancement of Science, the Adelis Foundation, J. L. and V. Schwartz, A. and G. Markovitz, A. and C. Adelson, the French National Centre for Scientific Research (CNRS), D. L. Schwarz, the V. R. Schwartz Research Fellow Chair, L. Steinberg, J. N. Halpern, A. Edelheit, grants funded by the European Research Council, a Marie Curie Integration grant, the German-Israeli Foundation for Scientific Research and Development, the Israel Science Foundation, the Minerva Foundation, the Rising Tide Foundation, the Helmholtz Foundation, and the European Foundation for the Study of Diabetes. E.E. is the incumbent of the Rina Gudinski Career Development Chair, a senior fellow of the Canadian Institute For Advanced Research (CIFAR) and a research scholar. E. E. is supported by the Bill and Melinda Gates Foundation and the Howard Hughes Medical Institute (HHMI).

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Zmora, N., Suez, J. & Elinav, E. You are what you eat: diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol 16, 35–56 (2019). https://doi.org/10.1038/s41575-018-0061-2

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