Bulldog Weight Loss The Role of Gut Health in Weight Management

Roles of the gut microbiome in weight management

1. WHO. Malnutrition. WHO https://www.who.int/news-room/fact-sheets/detail/malnutrition (2021).

2. WHO. Obesity and overweight. WHO https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (2021).

3. Popkin, B. M., Corvalan, C. & Grummer-Strawn, L. M. Dynamics of the double burden of malnutrition and the changing nutrition reality. Lancet 395, 6574 (2020).

   Article PubMed Google Scholar

4. Anastasiou, C. A., Karfopoulou, E. & Yannakoulia, M. Weight regaining: from statistics and behaviors to physiology and metabolism. Metabolism 64, 13951407 (2015).

   Article CAS PubMed Google Scholar

5. Johannsen, D. L. et al. Metabolic slowing with massive weight loss despite preservation of fat-free mass. J. Clin. Endocrinol. Metab. 97, 24892496 (2012).

   Article CAS PubMed PubMed Central Google Scholar

6. Fothergill, E. et al. Persistent metabolic adaptation 6 years after The Biggest Loser competition. Obesity 24, 16121619 (2016).

   Article PubMed Google Scholar

7. Guerrant, R. L., DeBoer, M. D., Moore, S. R., Scharf, R. J. & Lima, A. A. M. The impoverished gut a triple burden of diarrhoea, stunting and chronic disease. Nat. Rev. Gastroenterol. Hepatol. 10, 220229 (2013).

   Article PubMed Google Scholar

8. Veenendaal, M. V. E. et al. Transgenerational effects of prenatal exposure to the 194445 Dutch famine. Br. J. Obstet. Gynaecol. 120, 548554 (2013).

   Article CAS Google Scholar

9. Bckhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 1571815723 (2004).

   Article PubMed PubMed Central Google Scholar

10. 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 PubMed PubMed Central Google Scholar

11. Cox, L. M. & Blaser, M. J. Antibiotics in early life and obesity. Nat. Rev. Endocrinol. 11, 182190 (2014).

    Article PubMed PubMed Central Google Scholar

12. Cani, P. D. et al. Microbial regulation of organismal energy homeostasis. Nat. Metab. 1, 3446 (2019).

    Article CAS PubMed Google Scholar

13. Gilbert, J. A. et al. Current understanding of the human microbiome. Nat. Med. 24, 392400 (2018).

    Article CAS PubMed PubMed Central Google Scholar

14. Al-Asmakh, M. & Zadjali, F. Use of germ-free animal models in microbiota-related research. J. Microbiol. Biotechnol. 25, 15831588 (2015).

    Article PubMed Google Scholar

15. Gheorghe, C. E. et al. Investigating causality with fecal microbiota transplantation in rodents: applications, recommendations and pitfalls. Gut Microbes 13, 1941711 (2021).

    Article PubMed PubMed Central Google Scholar

16. Hayes, C. L. et al. Commensal microbiota induces colonic barrier structure and functions that contribute to homeostasis. Sci. Rep. 8, 14184 (2018).

    Article PubMed PubMed Central Google Scholar

17. Kawai, Y. & Morotomi, M. Intestinal enzyme activities in germfree, conventional, and gnotobiotic rats associated with indigenous microorganisms. Infect. Immun. 19, 771778 (1978).

    Article CAS PubMed PubMed Central Google Scholar

18. Slezak, K. et al. Association of germ-free mice with a simplified human intestinal microbiota results in a shortened intestine. Gut Microbes 5, 176182 (2014).

    Article PubMed PubMed Central Google Scholar

19. Fouladi, F. et al. Sequence variant analysis reveals poor correlations in microbial taxonomic abundance between humans and mice after gnotobiotic transfer. ISME J. 14, 18091820 (2020).

    Article CAS PubMed PubMed Central Google Scholar

20. Walter, J., Armet, A. M., Finlay, B. B. & Shanahan, F. Establishing or exaggerating causality for the gut microbiome: lessons from human microbiota-associated rodents. Cell 180, 221232 (2020).

    Article CAS PubMed Google Scholar

21. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 10271031 (2006). This study establishes that the gut microbiome differs between individuals who are lean and obese and that obese phenotypes are transmissible to gnotobiotic mice.

    Article PubMed Google Scholar

22. Li, M. et al. Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice. Nat. Commun. 13, 2060 (2022).

    Article CAS PubMed PubMed Central Google Scholar

23. Thaiss, C. A. et al. Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature 540, 544551 (2016). This study implicates microbiome contributions to weight regain after weight loss.

    Article CAS PubMed Google Scholar

24. Koren, O. et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150, 470480 (2012).

    Article CAS PubMed PubMed Central Google Scholar

25. Smith, M. I. et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548554 (2013). This study finds an immature gut microbiome configuration in a severe form of undernutrition.

    Article CAS PubMed PubMed Central Google Scholar

26. Subramanian, S. et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510, 417421 (2014).

    Article CAS PubMed PubMed Central Google Scholar

27. Liou, A. P. et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci. Transl Med. 5, 178ra41 (2013).

    Article PubMed PubMed Central Google Scholar

28. von Schwartzenberg, R. J. et al. Caloric restriction disrupts the microbiota and colonization resistance. Nature 595, 272277 (2021).

    Article Google Scholar

29. Carmody, R. N. et al. Cooking shapes the structure and function of the gut microbiome. Nat. Microbiol. 4, 20522063 (2019).

    Article PubMed PubMed Central Google Scholar

30. Cox, L. M. et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705721 (2014). This study shows that gut microbiome perturbations in early life can have long-term consequences even when signatures recover.

    Article CAS PubMed PubMed Central Google Scholar

31. McGuire, M. K. & McGuire, M. A. Microbiomes and childhood malnutrition: what is the evidence? Ann. Nutr. Metab. 77, 3648(2021).

    Article CAS Google Scholar

32. Vonaesch, P. et al. Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa. Proc. Natl Acad. Sci. USA 115, E8489E8498 (2018).

    Article CAS PubMed PubMed Central Google Scholar

33. Kimura, I. et al. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science 367, eaaw8429 (2020). This study demonstrates that exposure to SCFAs in utero alters development in a manner that protects against the adult metabolic consequences of a high-fat diet.

    Article CAS PubMed Google Scholar

34. Mishra, A. et al. Microbial exposure during early human development primes fetal immune cells. Cell 184, 33943409 (2021).

    Article CAS PubMed PubMed Central Google Scholar

35. Schulfer, A. F. et al. Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice. Nat. Microbiol. 3, 234242 (2018).

    Article CAS PubMed Google Scholar

36. Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560564 (2016).

    Article CAS PubMed Google Scholar

37. Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565569 (2016).

    Article CAS PubMed PubMed Central Google Scholar

38. Cotillard, A. et al. A posteriori dietary patterns better explain variations of the gut microbiome than individual markers in the American Gut Project. Am. J. Clin. Nutr. 115, 432443 (2022).

    Article PubMed Google Scholar

39. Asnicar, F. et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat. Med. 27, 321332 (2021). This study correlates microbiome composition with dietary records and metabolic panels, finding connections between specific microorganisms and health.

    Article CAS PubMed PubMed Central Google Scholar

40. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559563 (2014). This human study demonstrates that gut microbiome composition and function respond to diet within days of administration.

    Article CAS PubMed Google Scholar

41. Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105108 (2011).

    Article CAS PubMed PubMed Central Google Scholar

42. Oliver, A. et al. High-fiber, whole-food dietary intervention alters the human gut microbiome but not fecal short-chain fatty acids. mSystems 6, e00115e00121 (2021).

    Article CAS PubMed PubMed Central Google Scholar

43. Grembi, J. A. et al. Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention. Sci. Rep. 10, 1405 (2020). This study demonstrates that weight loss success was correlated with the extent of microbiome response to diet.

    Article CAS PubMed PubMed Central Google Scholar

44. Bisanz, J. E., Upadhyay, V., Turnbaugh, J. A., Ly, K. & Turnbaugh, P. J. Meta-analysis reveals reproducible gut microbiome alterations in response to a high-fat diet. Cell Host Microbe 26, 265272 (2019).

    Article CAS PubMed PubMed Central Google Scholar

45. Dalby, M. J., Ross, A. W., Walker, A. W. & Morgan, P. J. Dietary uncoupling of gut microbiota and energy harvesting from obesity and glucose tolerance in mice. Cell Rep. 21, 15211533 (2017).

    Article CAS PubMed PubMed Central Google Scholar

46. Ang, Q. Y. et al. Ketogenic diets alter the gut microbiome resulting in decreased intestinal Th17 cells. Cell 181, 12631275 (2020).

    Article CAS PubMed PubMed Central Google Scholar

47. Ge, L. et al. Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials. Br. Med. J. 369, m696 (2020).

    Article Google Scholar

48. Koh, A., De Vadder, F., Kovatcheva-Datchary, P. & Bckhed, F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165, 13321345 (2016). This review summarizes the origin and physiological functions of SCFAs.

    Article CAS PubMed Google Scholar

49. Sonnenburg, E. D. et al. Diet-induced extinctions in the gut microbiota compound over generations. Nature 529, 212215 (2016).

    Article CAS PubMed PubMed Central Google Scholar

50. Wastyk, H. C. et al. Gut-microbiota-targeted diets modulate human immune status. Cell 184, 41374153 (2021).

    Article CAS PubMed PubMed Central Google Scholar

51. Zhao, L. et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359, 11511156 (2018).

    Article CAS PubMed Google Scholar

52. Lancaster, S. M. et al. Global, distinctive, and personal changes in molecular and microbial profiles by specific fibers in humans. Cell Host Microbe 30, 848862 (2022).

    Article CAS PubMed PubMed Central Google Scholar

53. 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, 491502 (2017).

    Article PubMed Google Scholar

54. Baxter, N. T. et al. Dynamics of human gut microbiota and short-chain fatty acids in response to dietary interventions with three fermentable fibers. mBio 10, e02566-18 (2019).

    Article PubMed PubMed Central Google Scholar

55. Deehan, E. C. et al. Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production. Cell Host Microbe 27, 389404 (2020).

    Article CAS PubMed Google Scholar

56. Chassaing, B. et al. Randomized controlled-feeding study of dietary emulsifier carboxymethylcellulose reveals detrimental impacts on the gut microbiota and metabolome. Gastroenterology 162, 743756 (2022).

    Article CAS PubMed Google Scholar

57. Suez, J. et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181186 (2014). This study demonstrates that non-nutritive artificial sweeteners impacted microbiome composition with negative consequences for metabolic health.

    Article CAS PubMed Google Scholar

58. Chassaing, B. et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519, 9296 (2015). This study demonstrates that dietary emulsifiers compromise metabolic health via disruption of the gut microbiota and mucosal barrier.

    Article CAS PubMed PubMed Central Google Scholar

59. Bian, X. et al. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem. Toxicol. 107, 530539 (2017).

    Article CAS PubMed PubMed Central Google Scholar

60. Rodriguez-Palacios, A. et al. The artificial sweetener Splenda promotes gut Proteobacteria, dysbiosis, and myeloperoxidase reactivity in Crohns disease-like ileitis. Inflamm. Bowel Dis. 24, 10051020 (2018).

    Article PubMed PubMed Central Google Scholar

61. Suez, J. et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell 185, 33073328 (2022).

    Article CAS PubMed Google Scholar

62. Serrano, J. et al. High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome 9, 11 (2021).

    Article CAS PubMed PubMed Central Google Scholar

63. Thomson, P., Santibaez, R., Aguirre, C., Galgani, J. E. & Garrido, D. Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. Br. J. Nutr. 122, 856862 (2019).

    Article CAS PubMed Google Scholar

64. Cristofori, F. et al. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front. Immunol. 12, 578386 (2021).

    Article CAS PubMed PubMed Central Google Scholar

65. Tao, Y.-W., Gu, Y.-L., Mao, X.-Q., Zhang, L. & Pei, Y.-F. Effects of probiotics on type II diabetes mellitus: a meta-analysis. J. Transl Med. 18, 30 (2020).

    Article CAS PubMed PubMed Central Google Scholar

66. Kocsis, T. et al. Probiotics have beneficial metabolic effects in patients with type 2 diabetes mellitus: a meta-analysis of randomized clinical trials. Sci. Rep. 10, 11787 (2020).

    Article CAS PubMed PubMed Central Google Scholar

67. lvarez-Arrao, V. & Martn-Pelez, S. Effects of probiotics and synbiotics on weight loss in subjects with overweight or obesity: a systematic review. Nutrients 13, 3627 (2021).

    Article PubMed PubMed Central Google Scholar

68. Park, S. & Bae, J.-H. Probiotics for weight loss: a systematic review and meta-analysis. Nutr. Res. 35, 566575 (2015).

    Article CAS PubMed Google Scholar

69. Eales, J. et al. Is consuming yoghurt associated with weight management outcomes? Results from a systematic review. Int. J. Obes. 40, 731746 (2016).

    Article CAS Google Scholar

70. Lim, S., Moon, J. H., Shin, C. M., Jeong, D. & Kim, B. Effect of Lactobacillus sakei, a probiotic derived from kimchi, on body fat in Koreans with obesity: a randomized controlled study. Endocrinol. Metab. 35, 425434 (2020).

    Article CAS Google Scholar

71. Kapp, J. M. & Sumner, W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann. Epidemiol. 30, 6670 (2019).

    Article PubMed Google Scholar

72. Carmody, R. N. et al. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe 17, 7284 (2015).

    Article CAS PubMed Google Scholar

73. Christensen, L. et al. Prevotella abundance predicts weight loss success in healthy, overweight adults consuming a whole-grain diet ad libitum: a post hoc analysis of a 6-wk randomized controlled trial. J. Nutr. 149, 21742181 (2019).

    Article PubMed Google Scholar

74. Menni, C. et al. Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain. Int. J. Obes. 41, 10991105 (2017).

    Article CAS Google Scholar

75. Jian, C. et al. Gut microbiota predicts body fat change following a low-energy diet: a PREVIEW intervention study. Genome Med. 14, 54 (2022).

    Article CAS PubMed PubMed Central Google Scholar

76. Foster, K. R., Schluter, J., Coyte, K. Z. & Rakoff-Nahoum, S. The evolution of the host microbiome as an ecosystem on a leash. Nature 548, 4351 (2017).

    Article CAS PubMed PubMed Central Google Scholar

77. Carmody, R. N., Sarkar, A. & Reese, A. T. Gut microbiota through an evolutionary lens. Science 372, 462463 (2021).

    Article CAS PubMed Google Scholar

78. Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 10791094 (2015). This study shows that models incorporating the gut microbiome improved prediction of postprandial glycaemic response.

    Article CAS PubMed Google Scholar

79. Johnson, A. J. et al. Daily sampling reveals personalized dietmicrobiome associations in humans. Cell Host Microbe 25, 789802 (2019).

    Article CAS PubMed Google Scholar

80. Lai, Z.-L. et al. Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice. Sci. Rep. 8, 15625 (2018).

    Article PubMed PubMed Central Google Scholar

81. Cronin, O. et al. A prospective metagenomic and metabolomic analysis of the impact of exercise and/or whey protein supplementation on the gut microbiome of sedentary adults. mSystems 3, e00044-18 (2018).

    Article PubMed PubMed Central Google Scholar

82. Kang, S. S. et al. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol. Neurodegener. 9, 36 (2014).

    Article PubMed PubMed Central Google Scholar

83. Mohr, A. E. et al. The athletic gut microbiota. J. Int. Soc. Sports Nutr. 17, 24 (2020).

    Article PubMed PubMed Central Google Scholar

84. Allen, J. M. et al. Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice. J. Appl. Physiol. 118, 10591066 (2015).

    Article CAS PubMed Google Scholar

85. Matsumoto, M. et al. Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum. Biosci. Biotechnol. Biochem. 72, 572576 (2008).

    Article CAS PubMed Google Scholar

86. Allen, J. M. et al. Exercise alters gut microbiota composition and function in lean and obese humans. Med. Sci. Sports Exerc. 50, 747757 (2018).

    Article PubMed Google Scholar

87. Scheiman, J. et al. Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nat. Med. 25, 11041109 (2019). This study suggests that lactate-consuming, propionate-producing microorganisms positively influence exercise performance.

    Article CAS PubMed PubMed Central Google Scholar

88. Zhao, X. et al. Response of gut microbiota to metabolite changes induced by endurance exercise. Front. Microbiol. 9, 765 (2018).

    Article PubMed PubMed Central Google Scholar

89. Clarke, S. F. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63, 19131920 (2014).

    Article CAS PubMed Google Scholar

90. Barton, W. et al. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut 67, 625633 (2018).

    CAS PubMed Google Scholar

91. Petersen, L. M. et al. Community characteristics of the gut microbiomes of competitive cyclists. Microbiome 5, 98 (2017).

    Article PubMed PubMed Central Google Scholar

92. Durk, R. P. et al. Gut microbiota composition is related to cardiorespiratory fitness in healthy young adults. Int. J. Sport. Nutr. Exerc. Metab. 29, 249253 (2019).

    Article CAS PubMed Google Scholar

93. Estaki, M. et al. Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome 4, 42 (2016).

    Article PubMed PubMed Central Google Scholar

94. Morita, H. et al. Bacteroides uniformis and its preferred substrate, -cyclodextrin, enhance endurance exercise performance in mice and human males. Sci. Adv. 9, eadd2120 (2023).

    Article CAS PubMed PubMed Central Google Scholar

95. Liu, Y. et al. Gut microbiome fermentation determines the efficacy of exercise for diabetes prevention. Cell Metab. 31, 7791 (2020).

    Article CAS PubMed Google Scholar

96. Bressa, C. et al. Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLoS ONE 12, e0171352 (2017).

    Article PubMed PubMed Central Google Scholar

97. Munukka, E. et al. Six-week endurance exercise alters gut metagenome that is not reflected in systemic metabolism in over-weight women. Front. Microbiol. 9, 2323 (2018).

    Article PubMed PubMed Central Google Scholar

98. Carmody, R. N. & Baggish, A. L. Working out the bugs: microbial modulation of athletic performance. Nat. Metab. 1, 658659 (2019).

    Article PubMed Google Scholar

99. Hoffman-Goetz, L., Pervaiz, N., Packer, N. & Guan, J. Freewheel training decreases pro- and increases anti-inflammatory cytokine expression in mouse intestinal lymphocytes. Brain Behav. Immun. 24, 11051115 (2010).

    Article CAS PubMed Google Scholar

100. Ismail, A. S. et al. Intraepithelial lymphocytes are essential mediators of hostmicrobial homeostasis at the intestinal mucosal surface. Proc. Natl Acad. Sci. USA 108, 87438748 (2011).

     Article CAS PubMed PubMed Central Google Scholar

101. Jeukendrup, A. E. et al. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men. Clin. Sci. 98, 4755 (2000).

     Article CAS Google Scholar

102. Lira, F. S. et al. Endotoxin levels correlate positively with a sedentary lifestyle and negatively with highly trained subjects. Lipids Health Dis. 9, 82 (2010).

     Article PubMed PubMed Central Google Scholar

103. Meissner, M. et al. Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice. Atherosclerosis 218, 323329 (2011).

     Article CAS PubMed Google Scholar

104. Yardeni, T. et al. Host mitochondria influence gut microbiome diversity: a role for ROS. Sci. Signal. 12, eeaw3159 (2019).

     Article Google Scholar

105. Song, B. K., Cho, K. O., Jo, Y., Oh, J. W. & Kim, Y. S. Colon transit time according to physical activity level in adults. J. Neurogastroenterol. Motil. 18, 6469 (2012).

     Article PubMed PubMed Central Google Scholar

106. Asnicar, F. et al. Blue poo: impact of gut transit time on the gut microbiome using a novel marker. Gut 70, 16651674 (2021).

     Article CAS PubMed Google Scholar

107. van Wijck, K. et al. Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men. PLoS ONE 6, e22366 (2011).

     Article PubMed PubMed Central Google Scholar

108. Murphy, R. M., Watt, M. J. & Febbraio, M. A. Metabolic communication during exercise. Nat. Metab. 2, 805816 (2020).

     Article PubMed Google Scholar

109. OBrien, P. E. et al. Long-term outcomes after bariatric surgery: a systematic review and meta-analysis of weight loss at 10 or more years for all bariatric procedures and a single-centre review of 20-year outcomes after adjustable gastric banding. Obes. Surg. 29, 314 (2019).

     Article PubMed Google Scholar

110. Kong, L.-C. et al. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am. J. Clin. Nutr. 98, 1624 (2013).

     Article CAS PubMed Google Scholar

111. Paganelli, F. L. et al. Roux-Y gastric bypass and sleeve gastrectomy directly change gut microbiota composition independent of surgery type. Sci. Rep. 9, 10979 (2019).

     Article PubMed PubMed Central Google Scholar

112. Li, J. V. et al. Roux-en-Y gastric bypass-induced bacterial perturbation contributes to altered host-bacterial co-metabolic phenotype. Microbiome 9, 139 (2021).

     Article CAS PubMed PubMed Central Google Scholar

113. Tremaroli, V. et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 22, 228238 (2015).

     Article CAS PubMed PubMed Central Google Scholar

114. Shen, N. et al. Longitudinal changes of microbiome composition and microbial metabolomics after surgical weight loss in individuals with obesity. Surg. Obes. Relat. Dis. 15, 13671373 (2019).

     Article PubMed PubMed Central Google Scholar

115. Shantavasinkul, P. C., Omotosho, P., Corsino, L., Portenier, D. & Torquati, A. Predictors of weight regain in patients who underwent Roux-en-Y gastric bypass surgery. Surg. Obes. Relat. Dis. 12, 16401645 (2016).

     Article PubMed Google Scholar

116. Gutirrez-Repiso, C. et al. Gut microbiota specific signatures are related to the successful rate of bariatric surgery. Am. J. Transl Res. 11, 942952 (2019).

     PubMed PubMed Central Google Scholar

117. Fouladi, F. et al. The role of the gut microbiota in sustained weight loss following Roux-en-Y gastric bypass surgery. Obes. Surg. 29, 12591267 (2019).

     Article PubMed Google Scholar

118. Spanogiannopoulos, P., Bess, E. N., Carmody, R. N. & Turnbaugh, P. J. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat. Rev. Microbiol. 14, 273287 (2016).

     Article CAS PubMed PubMed Central Google Scholar

119. Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623628 (2018).

     Article CAS PubMed PubMed Central Google Scholar

120. Wu, H. et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23, 850858 (2017). This study establishes that interactions between metformin and the gut microbiome impact efficacy for diabetes treatment.

     Article CAS PubMed Google Scholar

121. Forslund, K. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528, 262266 (2015).

     Article CAS PubMed PubMed Central Google Scholar

122. Zhang, X. et al. Effects of acarbose on the gut microbiota of prediabetic patients: a randomized, double-blind, controlled crossover trial. Diabetes Ther. 8, 293307 (2017).

     Article CAS PubMed PubMed Central Google Scholar

123. Balaich, J. et al. The human microbiome encodes resistance to the antidiabetic drug acarbose. Nature 600, 110115 (2021).

     Article CAS PubMed PubMed Central Google Scholar

124. Vieira-Silva, S. et al. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature 581, 310315 (2020).

     Article CAS PubMed Google Scholar

125. Wilmanski, T. et al. Heterogeneity in statin responses explained by variation in the human gut microbiome. Med 3, 388405 (2022).

     Article CAS PubMed Google Scholar

126. Baunwall, S. M. D. et al. Faecal microbiota transplantation for recurrent Clostridioides difficile infection: an updated systematic review and meta-analysis. eClinicalMedicine 2930, 100642 (2020).

     Article PubMed PubMed Central Google Scholar

127. Imdad, A. et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst. Rev. 11, CD012774 (2018).

     PubMed Google Scholar

128. Yu, E. W. et al. Fecal microbiota transplantation for the improvement of metabolism in obesity: the FMT-TRIM double-blind placebo-controlled pilot trial. PLoS Med. 17, e1003051 (2020).

     Article PubMed PubMed Central Google Scholar

129. Leong, K. S. W. et al. Effects of fecal microbiome transfer in adolescents with obesity: the gut bugs randomized controlled trial. JAMA Netw. Open 3, e2030415 (2020).

     Article PubMed PubMed Central Google Scholar

130. Mocanu, V. et al. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial. Nat. Med. 27, 12721279 (2021).

     Article CAS PubMed Google Scholar

131. Rinott, E. et al. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain. Gastroenterology 160, 158173 (2021). This study demonstrates the potential for self-faecal transplant combined with diet to improve the maintenance of weight loss.

     Article CAS PubMed Google Scholar

132. Rinott, E. et al. Autologous fecal microbiota transplantation can retain the metabolic achievements of dietary interventions. Eur. J. Intern. Med. 92, 1723 (2021).

     Article CAS PubMed Google Scholar

133. 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, 107113 (2017).

     Article CAS PubMed Google Scholar

134. Depommier, C. et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 25, 10961103 (2019). This human intervention study shows that daily A. muciniphila supplementation had beneficial effects on metabolic health.

     Article CAS PubMed PubMed Central Google Scholar

135. Yoon, H. S. et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat. Microbiol. 6, 563573 (2021).

     Article CAS PubMed Google Scholar

136. Bae, M. et al. Akkermansia muciniphila phospholipid induces homeostatic immune responses. Nature 608, 168173 (2022).

     Article CAS PubMed PubMed Central Google Scholar

137. Beresford-Jones, B. S. et al. The mouse gastrointestinal bacteria catalogue enables translation between the mouse and human gut microbiotas via functional mapping. Cell Host Microbe 30, 124138 (2022).

     Article CAS PubMed PubMed Central Google Scholar

138. 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, 220230 (2012).

     Article CAS PubMed PubMed Central Google Scholar

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

     Article PubMed PubMed Central Google Scholar

140. Arnold, J. W., Roach, J. & Azcarate-Peril, M. A. Emerging technologies for gut microbiome research. Trends Microbiol. 24, 887901 (2016).

     Article CAS PubMed PubMed Central Google Scholar

141. Yu, H. et al. The contributions of human mini-intestines to the study of intestinal physiology and pathophysiology. Annu. Rev. Physiol. 79, 291312 (2017).

     Article CAS PubMed PubMed Central Google Scholar

142. Karcher, N. et al. Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly. Genome Biol. 22, 209 (2021).

     Article CAS PubMed PubMed Central Google Scholar

143. Liu, Q. et al. Akkermansia muciniphila exerts strain-specific effects on DSS-induced ulcerative colitis in mice. Front. Cell. Infect. Microbiol. 11, 698914 (2021).

     Article CAS PubMed PubMed Central Google Scholar

144. Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 570, 462467 (2019).

     Article CAS PubMed PubMed Central Google Scholar

145. Haiser, H. J. et al. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341, 295298 (2013).

     Article CAS PubMed PubMed Central Google Scholar

146. Wallace, B. D. et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330, 831835 (2010).

     Article CAS PubMed PubMed Central Google Scholar

147. Maini Rekdal, V., Bess, E. N., Bisanz, J. E., Turnbaugh, P. J. & Balskus, E. P. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science 364, eaau6323 (2019).

     Article PubMed Google Scholar

148. Gough, E. K. et al. Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota. Microbiome 3, 24 (2015).

     Article PubMed PubMed Central Google Scholar

149. Raman, A. S. et al. A sparse covarying unit that describes healthy and impaired human gut microbiota development. Science 365, eaau4735 (2019).

     Article PubMed PubMed Central Google Scholar

150. Gehrig, J. L. et al. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science 365, eaau4732 (2019).

     Article PubMed PubMed Central Google Scholar

151. Chen, R. Y. et al. A microbiota-directed food intervention for undernourished children. N. Engl. J. Med. 384, 15171528 (2021). This trial shows that a microbiota-targeted dietary intervention could improve health in undernourished children.

     Article PubMed PubMed Central Google Scholar

152. Semova, I. et al. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish. Cell Host Microbe 12, 277288 (2012).

     Article CAS PubMed Google Scholar

153. Martinez-Guryn, K. et al. Small intestine microbiota regulate host digestive and absorptive adaptive responses to dietary lipids. Cell Host Microbe 23, 458469 (2018).

     Article CAS PubMed PubMed Central Google Scholar

154. Chadaideh, K. S. & Carmody, R. N. Hostmicrobial interactions in the metabolism of different dietary fats. Cell Metab. 33, 857872 (2021).

     Article CAS PubMed Google Scholar

155. Carmody, R. N. & Wrangham, R. W. The energetic significance of cooking. J. Hum. Evol. 57, 379391 (2009).

     Article PubMed Google Scholar

156. Carmody, R. N., Weintraub, G. S. & Wrangham, R. W. Energetic consequences of thermal and nonthermal food processing. Proc. Natl Acad. Sci. USA 108, 1919919203 (2011).

     Article CAS PubMed PubMed Central Google Scholar

157. Cummings, J. H. & Macfarlane, G. T. Role of intestinal bacteria in nutrient metabolism. Clin. Nutr. 16, 311 (1997).

     Article Google Scholar

158. McNeil, N. I. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 39, 338342 (1984).

     Article CAS PubMed Google Scholar

159. den Besten, G. et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPAR-dependent switch from lipogenesis to fat oxidation. Diabetes 64, 23982408 (2015).

     Article Google Scholar

160. Lu, Y. et al. Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating G protein-coupled receptors and gut microbiota. Sci. Rep. 6, 37589 (2016).

     Article CAS PubMed PubMed Central Google Scholar

161. van der Hee, B. & Wells, J. M. Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol. 29, 700712 (2021).

     Article PubMed Google Scholar

162. Hong, Y.-H. et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146, 50925099 (2005).

     Article CAS PubMed Google Scholar

163. Jocken, J. W. E. et al. Short-chain fatty acids differentially affect intracellular lipolysis in a human white adipocyte model. Front. Endocrinol. 8, 372 (2017).

     Article Google Scholar

164. Jia, Y. et al. Butyrate stimulates adipose lipolysis and mitochondrial oxidative phosphorylation through histone hyperacetylation-associated ₃-adrenergic receptor activation in high-fat diet-induced obese mice. Exp. Physiol. 102, 273281 (2017).

     Article PubMed Google Scholar

165. Gao, Z. et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 15091517 (2009).

     Article CAS PubMed PubMed Central Google Scholar

166. Cummings, J. H. & Macfarlane, G. T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70, 443459 (1991).

     Article CAS PubMed Google Scholar

167. De Vadder, F. et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 8496 (2014).

     Article PubMed Google Scholar

168. Kondo, T., Kishi, M., Fushimi, T. & Kaga, T. Acetic acid upregulates the expression of genes for fatty acid oxidation enzymes in liver to suppress body fat accumulation. J. Agric. Food Chem. 57, 59825986 (2009).

     Article CAS PubMed Google Scholar

169. Sahuri-Arisoylu, M. et al. Reprogramming of hepatic fat accumulation and browning of adipose tissue by the short-chain fatty acid acetate. Int. J. Obes. 40, 955963 (2016).

     Article CAS Google Scholar

170. Sinal, C. J. et al. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102, 731744 (2000).

     Article CAS PubMed Google Scholar

171. Ridlon, J. M., Kang, D. J., Hylemon, P. B. & Bajaj, J. S. Bile acids and the gut microbiome. Curr. Opin. Gastroenterol. 30, 332338 (2014).

     Article PubMed PubMed Central Google Scholar

172. Pathak, P. et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology 68, 15741588 (2018).

     Article CAS PubMed Google Scholar

173. 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, 17441754 (2015).

     Article CAS PubMed Google Scholar

174. Goswami, C., Iwasaki, Y. & Yada, T. Short-chain fatty acids suppress food intake by activating vagal afferent neurons. J. Nutr. Biochem. 57, 130135 (2018).

     Article CAS PubMed Google Scholar

175. Tolhurst, G. et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364371 (2012).

     Article CAS PubMed PubMed Central Google Scholar

176. Psichas, A. et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. 39, 424429 (2015).

     Article CAS Google Scholar

177. 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

178. Hsiao, W. W. L., Metz, C., Singh, D. P. & Roth, J. The microbes of the intestine: an introduction to their metabolic and signaling capabilities. Endocrinol. Metab. Clin. North. Am. 37, 857871 (2008).

     Article CAS PubMed PubMed Central Google Scholar

179. Strandwitz, P. Neurotransmitter modulation by the gut microbiota. Brain Res. 1693, 128133 (2018).

     Article CAS PubMed PubMed Central Google Scholar

180. Yano, J. M. et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264276 (2015).

     Article CAS PubMed PubMed Central Google Scholar

181. Heijtz, R. D. et al. Normal gut microbiota modulates brain development and behavior. Proc. Natl Acad. Sci. USA 108, 30473052 (2011).

     Article CAS PubMed Central Google Scholar

182. Swartz, T. D., Duca, F. A., de Wouters, T., Sakar, Y. & Covasa, M. Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota. Br. J. Nutr. 107, 621630 (2012).

     Article CAS PubMed Google Scholar

183. Duca, F. A., Swartz, T. D., Sakar, Y. & Covasa, M. Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota. PLoS ONE 7, e39748 (2012).

     Article CAS PubMed PubMed Central Google Scholar

184. de Wouters dOplinter, A. et al. Gut microbes participate in food preference alterations during obesity. Gut Microbes 13, 1959242 (2021).

     Article PubMed PubMed Central Google Scholar

185. Trevelline, B. K. & Kohl, K. D. The gut microbiome influences host diet selection behavior. Proc. Natl Acad. Sci. USA 119, e2117537119 (2022).

     Article CAS PubMed PubMed Central Google Scholar

186. Alcock, J., Maley, C. C. & Aktipis, C. A. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. Bioessays 36, 940949 (2014).

     Article PubMed PubMed Central Google Scholar

187. Leito-Gonalves, R. et al. Commensal bacteria and essential amino acids control food choice behavior and reproduction. PLoS Biol. 15, e2000862 (2017).

     Article PubMed PubMed Central Google Scholar

188. Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860867 (2006).

     Article CAS PubMed Google Scholar

189. Renz, H. & Skevaki, C. Early life microbial exposures and allergy risks: opportunities for prevention. Nat. Rev. Immunol. 21, 177191 (2021).

     Article CAS PubMed Google Scholar

190. Pronovost, G. N. & Hsiao, E. Y. Perinatal interactions between the microbiome, immunity, and neurodevelopment. Immunity 50, 1836 (2019).

     Article CAS PubMed PubMed Central Google Scholar

191. Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 17611772 (2007).

     Article CAS PubMed Google Scholar

192. Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science 328, 228231 (2010).

     Article CAS PubMed PubMed Central Google Scholar

193. Camilleri, M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 68, 15161526 (2019).

     Article CAS PubMed Google Scholar

194. Rohr, M. W., Narasimhulu, C. A., Rudeski-Rohr, T. A. & Parthasarathy, S. Negative effects of a high-fat diet on intestinal permeability: a review. Adv. Nutr. 11, 7791 (2020).

     Article PubMed Google Scholar