Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Leveraging diet to engineer the gut microbiome

Abstract

Autoimmune diseases, including inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, have distinct clinical presentations but share underlying patterns of gut microbiome perturbation and intestinal barrier dysfunction. Their potentially common microbial drivers advocate for treatment strategies aimed at restoring appropriate microbiome function, but individual variation in host factors makes a uniform approach unlikely. In this Perspective, we consolidate knowledge on diet–microbiome interactions in local inflammation, gut microbiota imbalance and host immune dysregulation. By understanding and incorporating the effects of individual dietary components on microbial metabolic output and host physiology, we examine the potential for diet-based therapies for autoimmune disease prevention and treatment. We also discuss tools targeting the gut microbiome, such as faecal microbiota transplantation, probiotics and orthogonal niche engineering, which could be optimized using custom dietary interventions. These approaches highlight paths towards leveraging diet for precise engineering of the gut microbiome at a time of increasing autoimmune disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Temporal trends in human host, the gut microbiome and diet.
Fig. 2: Diet–gut microbiome–host axis in autoimmune diseases and homeostasis.
Fig. 3: Approaches for personalized application of gut microbiome engineering tools.

Similar content being viewed by others

References

  1. Bach, J. F. The effect of infections on susceptibility to autoimmune and allergic diseases. N. Engl. J. Med. 347, 911–920 (2002).

    PubMed  Google Scholar 

  2. Markle, J. G. M. et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 339, 1084–1088 (2013).

    CAS  PubMed  Google Scholar 

  3. Inshaw, J. R. J., Cutler, A. J., Burren, O. S., Stefana, M. I. & Todd, J. A. Approaches and advances in the genetic causes of autoimmune disease and their implications. Nat. Immunol. 19, 674–684 (2018).

    CAS  PubMed  Google Scholar 

  4. Thorburn, A. N., Macia, L. & Mackay, C. R. Diet, metabolites, and “western-lifestyle” inflammatory diseases. Immunity 40, 833–842 (2014).

    CAS  PubMed  Google Scholar 

  5. Bach, J. F. The hygiene hypothesis in autoimmunity: the role of pathogens and commensals. Nat. Rev. Immunol. 18, 105–120 (2018).

    CAS  PubMed  Google Scholar 

  6. Levy, M., Kolodziejczyk, A. A., Thaiss, C. A. & Elinav, E. Dysbiosis and the immune system. Nat. Rev. Immunol. 17, 219–232 (2017).

    CAS  PubMed  Google Scholar 

  7. Fugger, L., Jensen, L. T. & Rossjohn, J. Challenges, progress, and prospects of developing therapies to treat autoimmune diseases. Cell 181, 63–80 (2020).

    CAS  PubMed  Google Scholar 

  8. Ananthakrishnan, A. N. et al. Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases. Cell Host Microbe 21, 603–610.e3 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Doherty, M. K. et al. Fecal microbiota signatures are associated with response to ustekinumab therapy among Crohn’s disease patients. mBio 9, e02120-17 (2018).

    PubMed  PubMed Central  Google Scholar 

  10. Scher, J. U., Nayak, R. R., Ubeda, C., Turnbaugh, P. J. & Abramson, S. B. Pharmacomicrobiomics in inflammatory arthritis: gut microbiome as modulator of therapeutic response. Nat. Rev. Rheumatol. 16, 282–292 (2020).

    PubMed  Google Scholar 

  11. Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res. 30, 492–506 (2020).

    PubMed  PubMed Central  Google Scholar 

  12. Wasko, N. J., Nichols, F. & Clark, R. B. Multiple sclerosis, the microbiome, TLR2, and the hygiene hypothesis. Autoimmun. Rev. 19, 102430 (2020).

    CAS  PubMed  Google Scholar 

  13. Ruff, W. E., Greiling, T. M. & Kriegel, M. A. Host–microbiota interactions in immune-mediated diseases. Nat. Rev. Microbiol. 18, 521–538 (2020).

    CAS  PubMed  Google Scholar 

  14. Cekanaviciute, E. et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc. Natl Acad. Sci. USA 114, 10713–10718 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Khalili, H. et al. The role of diet in the aetiopathogenesis of inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 15, 525–535 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Willett, W. et al. Food in the Anthropocene: the EAT–Lancet Commission on healthy diets from sustainable food systems. Lancet 393, 447–492 (2019).

    PubMed  Google Scholar 

  17. Cordain, L. et al. Origins and evolution of the Western diet: health implications for the 21st century. Am. J. Clin. Nutr. 81, 341–354 (2005).

    CAS  PubMed  Google Scholar 

  18. Kaoutari, A. E., Armougom, F., Gordon, J. I., Raoult, D. & Henrissat, B. The abundance and variety of carbohydrate-active enzymes in the human gut microbiota. Nat. Rev. Microbiol. 11, 497–504 (2013).

    PubMed  Google Scholar 

  19. Smits, S. A. et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania. Science 357, 802–806 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lombard, V., Golaconda, R. H., Drula, E., Coutinho, P. & Henrissat, B. BT2824 – the carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res 42, D490–D495 (2014).

    CAS  PubMed  Google Scholar 

  21. Manzel, A. et al. Role of ‘western diet’ in inflammatory autoimmune diseases. Curr. Allergy Asthma Rep. 14, 404 (2014).

    PubMed  PubMed Central  Google Scholar 

  22. Konijeti, G. G. et al. Efficacy of the autoimmune protocol diet for inflammatory bowel disease. Inflamm. Bowel Dis. 23, 2054–2060 (2017).

    PubMed  Google Scholar 

  23. Damas, O. M., Garces, L. & Abreu, M. T. Diet as adjunctive treatment for inflammatory bowel disease: review and update of the latest literature. Curr. Treat. Options Gastroenterol. 17, 313–325 (2019).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Chandrasekaran, A. et al. The autoimmune protocol diet modifies intestinal RNA expression in inflammatory bowel disease. Crohns Colitis 360 1, otz016 (2019).

    PubMed  PubMed Central  Google Scholar 

  26. Klein, E. Y. et al. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc. Natl Acad. Sci. USA 115, e3463–e3470 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Postler, T. S. & Ghosh, S. Understanding the holobiont: how microbial metabolites affect human health and shape the immune system. Cell Metab. 26, 110–130 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Camilleri, M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 68, 1516–1526 (2019).

    CAS  PubMed  Google Scholar 

  29. Paray, B. A., Albeshr, M. F., Jan, A. T. & Rather, I. A. Leaky gut and autoimmunity: an intricate balance in individuals health and the diseased state. Int. J. Mol. Sci. 21, 9770 (2020).

    CAS  PubMed Central  Google Scholar 

  30. Li, B., Selmi, C., Tang, R., Gershwin, M. E. & Ma, X. The microbiome and autoimmunity: a paradigm from the gut–liver axis. Cell. Mol. Immunol. 15, 595–609 (2018).

    PubMed  PubMed Central  Google Scholar 

  31. Márquez, A. et al. Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations. Genome Med. 10, 97 (2018).

    PubMed  PubMed Central  Google Scholar 

  32. Kolodziejczyk, A. A., Zheng, D. & Elinav, E. Diet–microbiota interactions and personalized nutrition. Nat. Rev. Microbiol. 17, 742–753 (2019).

    CAS  PubMed  Google Scholar 

  33. Inda, M. E., Broset, E., Lu, T. K. & de la Fuente-Nunez, C. Emerging Frontiers in Microbiome Engineering. Trends Immunol. 40, 952–973 (2019).

    CAS  PubMed  Google Scholar 

  34. Ruder, W. C., Lu, T. & Collins, J. J. Synthetic biology moving into the clinic. Science 333, 1248–1252 (2011).

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  36. Asnicar, F. et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat. Med. 27, 321–332 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Parker, A., Fonseca, S. & Carding, S. R. Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut Microbes 11, 135–157 (2020).

    PubMed  Google Scholar 

  38. Cox, L. M. et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705–721 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Al Nabhani, Z. et al. A weaning reaction to microbiota is required for resistance to immunopathologies in the adult. Immunity 50, 1276–1288.e5 (2019).

    CAS  PubMed  Google Scholar 

  40. Kalbermatter, C., Fernandez Trigo, N., Christensen, S. & Ganal-Vonarburg, S. C. Maternal microbiota, early life colonization and breast milk drive immune development in the newborn. Front. Immunol. 12, 683022 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Bokulich, N. A. et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci. Transl. Med. 8, 343ra82 (2016).

    PubMed  PubMed Central  Google Scholar 

  42. Mahmoud, T. I. et al. Autoimmune manifestations in aged mice arise from early-life immune dysregulation. Sci. Transl. Med. 8, 361ra137 (2016).

    PubMed  PubMed Central  Google Scholar 

  43. Vatanen, T. et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature 562, 589–594 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Lawson, M. A. E. et al. Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem. ISME J. 14, 635–648 (2020).

    CAS  PubMed  Google Scholar 

  45. Fanning, S. et al. Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection. Proc. Natl Acad. Sci. USA 109, 2108–2113 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Beaumont, M. et al. Gut microbiota derived metabolites contribute to intestinal barrier maturation at the suckling-to-weaning transition. Gut Microbes 11, 1268–1286 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Zegarra-Ruiz, D. F. et al. A diet-sensitive commensal lactobacillus strain mediates TLR7-dependent systemic autoimmunity. Cell Host Microbe 25, 113–127.e6 (2019).

    CAS  PubMed  Google Scholar 

  48. D’Hennezel, E., Abubucker, S., Murphy, L. O. & Cullen, T. W. Total lipopolysaccharide from the human gut microbiome silences toll-like receptor signaling. mSystems 2, e00046-17 (2017).

    PubMed  PubMed Central  Google Scholar 

  49. Fujiwara, M. et al. Enhanced TLR2 responses in multiple sclerosis. Clin. Exp. Immunol. 193, 313–326 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011).

    CAS  PubMed  Google Scholar 

  51. Ohkura, N. et al. Regulatory T cell-specific epigenomic region variants are a key determinant of susceptibility to common autoimmune diseases. Immunity 52, 1119–1132.e4 (2020).

    CAS  PubMed  Google Scholar 

  52. Lee, J. S. et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity 43, 727–738 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Cosorich, I. et al. High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis. Sci. Adv. 3, e1700492 (2017).

    PubMed  PubMed Central  Google Scholar 

  54. Buscarinu M. C. et al. Altered intestinal permeability in patients with relapsing–remitting multiple sclerosis: a pilot study. Mult. Scler. 23, 442–446 (2017).

    PubMed  Google Scholar 

  55. Zhang, X., Chen, B. D., Zhao, L. D. & Li, H. The gut microbiota: emerging evidence in autoimmune diseases. Trends Mol. Med. 26, 862–873 (2020).

    CAS  PubMed  Google Scholar 

  56. Deehan, E. C. et al. Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production. Cell Host Microbe 27, 389–404.e6 (2020).

    CAS  PubMed  Google Scholar 

  57. Swanson, K. S. et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat. Rev. Gastroenterol. Hepatol. 17, 687–701 (2020).

    PubMed  PubMed Central  Google Scholar 

  58. Hvas, C. L. et al. Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent clostridium difficile infection. Gastroenterology 156, 1324–1332.e3 (2019).

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  60. 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).

    CAS  PubMed  Google Scholar 

  61. Venkataraman, A. et al. Variable responses of human microbiomes to dietary supplementation with resistant starch. Microbiome 4, 33 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Sheflin, A. M., Melby, C. L., Carbonero, F. & Weir, T. L. Linking dietary patterns with gut microbial composition and function. Gut Microbes 8, 113–129 (2017).

    CAS  PubMed  Google Scholar 

  63. Vangay, P. et al. US immigration westernizes the human gut microbiome. Cell 175, 962–972.e10 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Johnson, A. J. et al. Daily sampling reveals personalized diet-microbiome associations in humans. Cell Host Microbe 25, 789–802.e5 (2019).

    CAS  PubMed  Google Scholar 

  65. Makki, K., Deehan, E. C., Walter, J. & Bäckhed, F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 23, 705–715 (2018).

    CAS  PubMed  Google Scholar 

  66. McNulty, N. P. et al. Effects of diet on resource utilization by a model human gut microbiota containing bacteroides cellulosilyticus WH2, a symbiont with an extensive glycobiome. PLoS Biol. 11, e1001637 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Flint, H. J., Scott, K. P., Duncan, S. H., Louis, P. & Forano, E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3, 289–306 (2012).

    PubMed  PubMed Central  Google Scholar 

  68. Tanes, C. et al. Role of dietary fiber in the recovery of the human gut microbiome and its metabolome. Cell Host Microbe 29, 394–407.e5 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Déjean, G. et al. Synergy between cell surface glycosidases and glycan-binding proteins dictates the utilization of specific beta(1,3)-glucans by human gut Bacteroides. mBio 11, e00095-20 (2020).

    PubMed  PubMed Central  Google Scholar 

  70. Desai, M. S. et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 1339–1353.e21 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Ananthakrishnan, A. N. Epidemiology and risk factors for IBD. Nat. Rev. Gastroenterol. Hepatol. 12, 205–217 (2015).

    PubMed  Google Scholar 

  72. So, D. et al. Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis. Am. J. Clin. Nutr. 107, 965–983 (2018).

    PubMed  Google Scholar 

  73. Liu, F. et al. Fructooligosaccharide (FOS) and galactooligosaccharide (GOS) increase Bifidobacterium but reduce butyrate producing bacteria with adverse glycemic metabolism in healthy young population. Sci. Rep. 7, 11789 (2017).

    PubMed  PubMed Central  Google Scholar 

  74. Valcheva, R. et al. Inulin-type fructans improve active ulcerative colitis associated with microbiota changes and increased short-chain fatty acids levels. Gut Microbes 10, 334–357 (2019).

    CAS  PubMed  Google Scholar 

  75. Salyers, A. A., West, S. E. H., Vercellotti, J. R. & Wilkins, T. D. Fermentation of mucins and plant polysaccharides by anaerobic bacteria from the human colon. Appl. Environ. Microbiol. 34, 529–533 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Chung, W. S. F. et al. Modulation of the human gut microbiota by dietary fibres occurs at the species level. BMC Biol. 14, 3 (2016).

    PubMed  PubMed Central  Google Scholar 

  77. Goodman, A. L. et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc. Natl Acad. Sci. USA 108, 6252–6257 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Elzinga, J., van der Oost, J., de Vos, W. M. & Smidt, H. The use of defined microbial communities to model host-microbe interactions in the human gut. Microbiol. Mol. Biol. Rev. 83, e00054-18 (2019).

    PubMed  PubMed Central  Google Scholar 

  79. 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 

  80. Singh, V. et al. Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer. Cell 175, 679–394.e22 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Yao, C. K. & Staudacher, H. M. The low-fibre diet: contender in IBD, or has it had its time? Lancet Gastroenterol. Hepatol. 4, 339 (2019).

    PubMed  Google Scholar 

  82. Wastyk, H. C. et al. Gut microbiota-targeted diets modulate human immune status. Cell 184, 4137–4153 (2020).

    Google Scholar 

  83. Ananthakrishnan, A. N. et al. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology 145, 970–977 (2013).

    CAS  PubMed  Google Scholar 

  84. Andersen, V. et al. Fibre intake and the development of inflammatory bowel disease: a European prospective multi-centre cohort study (EPIC-IBD). J. Crohns Colitis 12, 129–136 (2018).

    PubMed  Google Scholar 

  85. Machiels, K. et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63, 1275–1283 (2014).

    CAS  PubMed  Google Scholar 

  86. Earley, H., Lennon, G., Coffey, J. C., Winter, D. C. & O’Connell, P. R. Colonisation of the colonic mucus gel layer with butyrogenic and hydrogenotropic bacteria in health and ulcerative colitis. Sci. Rep. 11, 7262 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Venegas, D. P. et al. Short chain fatty acids (SCFAs) mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol. 10, 277 (2019).

    CAS  Google Scholar 

  88. Wong, A. C. & Levy, M. New approaches to microbiome-based therapies. mSystems 4, e00122-19 (2019).

    PubMed  PubMed Central  Google Scholar 

  89. Salminen, S. et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat. Rev. Gastroenterol. Hepatol. https://doi.org/10.1038/s41575-021-00440-6 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  90. 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).

    PubMed  PubMed Central  Google Scholar 

  91. Sünderhauf, A. et al. Loss of mucosal p32/gC1qR/HABP1 triggers energy deficiency and impairs goblet cell differentiation in ulcerative colitis. Cell. Mol. Gastroenterol. Hepatol. 12, 229–250 (2021).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Zeng, M. Y., Inohara, N. & Nuñez, G. Mechanisms of inflammation-driven bacterial dysbiosis in the gut. Mucosal Immunol. 10, 18–26 (2017).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  95. Louis, P. & Flint, H. J. Formation of propionate and butyrate by the human colonic microbiota. Environ. Microbiol. 19, 29–41 (2017).

    CAS  PubMed  Google Scholar 

  96. Duscha, A. et al. Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism. Cell 180, 1067–1080.e16 (2020).

    CAS  PubMed  Google Scholar 

  97. Cohen, A. B. et al. Dietary patterns and self-reported associations of diet with symptoms of inflammatory bowel disease. Dig. Dis. Sci. 58, 1322–1328 (2013).

    CAS  PubMed  Google Scholar 

  98. Levine, A. et al. Crohn’s disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial. Gastroenterology 157, 440–450.e8 (2019).

    PubMed  Google Scholar 

  99. Horwat, P. et al. Influence of enteral nutrition on gut microbiota composition in patients with Crohn’s disease: a systematic review. Nutrients 12, 2551 (2020).

    CAS  PubMed Central  Google Scholar 

  100. Walton, C. et al. Enteral feeding reduces metabolic activity of the intestinal microbiome in Crohn’s disease: an observational study. Eur. J. Clin. Nutr. 70, 1052–1056 (2016).

    CAS  PubMed  Google Scholar 

  101. Cignarella, F. et al. Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab. 27, 1222–1235.e6 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Wang, H. et al. Dietary non-digestible polysaccharides ameliorate intestinal epithelial barrier dysfunction in IL-10 knockout mice. J. Crohns Colitis 10, 1076–1086 (2016).

    PubMed  Google Scholar 

  103. Richards, J. L., Yap, Y. A., McLeod, K. H., MacKay, C. R. & Marinõ, E. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin. Transl. Immunol. 5, e82 (2016).

    Google Scholar 

  104. Macfarlane, G. T., Gibson, G. R., Beatty, E. & Cummings, J. H. Estimation of short-chain fatty acid production from protein by human intestinal bacteria based on branched-chain fatty acid measurements. FEMS Microbiol. Lett. 101, 81–88 (1992).

    CAS  Google Scholar 

  105. Llewellyn, S. R. et al. Interactions between diet and the intestinal microbiota alter intestinal permeability and colitis severity in mice. Gastroenterology 154, 1037–1046.e2 (2018).

    PubMed  Google Scholar 

  106. Kostovcikova, K. et al. Diet rich in animal protein promotes pro-inflammatory macrophage response and exacerbates colitis in mice. Front. Immunol. 10, 919 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Dallas, D. C. et al. Personalizing protein nourishment. Crit. Rev. Food Sci. Nutr. 57, 3313–3331 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Portune, K. J. et al. Gut microbiota role in dietary protein metabolism and health-related outcomes: the two sides of the coin. Trends Food Sci. Technol. 57, 213–232 (2016).

    CAS  Google Scholar 

  109. Gibson, G. R., Cummings, J. H. & Macfarlane, G. T. Growth and activities of sulphate-reducing bacteria in gut contents of healthy subjects and patients with ulcerative colitis. FEMS Microbiol. Lett. 86, 103–111 (1991).

    CAS  Google Scholar 

  110. Sridharan, G. V. et al. Prediction and quantification of bioactive microbiota metabolites in the mouse gut. Nat. Commun. 5, 5492 (2014).

    CAS  PubMed  Google Scholar 

  111. Agus, A., Planchais, J. & Sokol, H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe 23, 716–724 (2018).

    CAS  PubMed  Google Scholar 

  112. Lamas, B. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat. Med. 22, 598–605 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Islam, J. et al. Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice. J. Nutr. Biochem. 42, 43–50 (2017).

    CAS  PubMed  Google Scholar 

  114. Kepert, I. et al. D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease. J. Allergy Clin. Immunol. 139, 1525–1535 (2017).

    CAS  PubMed  Google Scholar 

  115. Sonner, J. K. et al. Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology. Nat. Commun. 10, 4877 (2019).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Watanabe, M., Fukiya, S. & Yokota, A. Comprehensive evaluation of the bactericidal activities of free bile acids in the large intestine of humans and rodents. J. Lipid Res. 58, 1143–1152 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Casadevall, A. The pathogenic potential of a microbe. mSphere 2, e00015-17 (2017).

    PubMed  PubMed Central  Google Scholar 

  119. Holscher, H. D. et al. Walnut consumption alters the gastrointestinal microbiota, microbially derived secondary bile acids, and health markers in healthy adults: a randomized controlled trial. J. Nutr. 148, 861–867 (2018).

    PubMed  PubMed Central  Google Scholar 

  120. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Cani, P. D. et al. Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes 55, 1484–1490 (2006).

    CAS  PubMed  Google Scholar 

  122. Vatanen, T. et al. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165, 842–853 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Steimle, A. et al. Weak agonistic LPS restores intestinal immune homeostasis. Mol. Ther. 27, 1974–1991 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Ang, Q. Y. et al. Ketogenic diets alter the gut microbiome resulting in decreased intestinal Th17 cells. Cell 181, 1263–1275.e16 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Lam, Y. Y. et al. Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice. Obesity 23, 1429–1439 (2015).

    CAS  PubMed  Google Scholar 

  126. Wolters, M. et al. Dietary fat, the gut microbiota, and metabolic health–a systematic review conducted within the MyNewGut project. Clin. Nutr. 38, 2504–2520 (2019).

    PubMed  Google Scholar 

  127. 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).

    PubMed  PubMed Central  Google Scholar 

  128. Watson, H. et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut 67, 1974–1983 (2018).

    CAS  PubMed  Google Scholar 

  129. Tindall, A. M., McLimans, C. J., Petersen, K. S., Kris-Etherton, P. M. & Lamendella, R. Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease. J. Nutr. 150, 806–817 (2020).

    PubMed  Google Scholar 

  130. Swidsinski, A. et al. Reduced mass and diversity of the colonic microbiome in patients with multiple sclerosis and their improvement with ketogenic diet. Front. Microbiol. 8, 1141 (2017).

    PubMed  PubMed Central  Google Scholar 

  131. Kong, C. et al. Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome. Signal. Transduct. Target. Ther. 6, 154 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Ni, F.-F. et al. The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy. Seizure 38, 17–22 (2016).

    PubMed  Google Scholar 

  133. Monteiro, C. A. et al. Ultra-processed foods: what they are and how to identify them. Public. Health Nutr. 22, 936–941 (2019).

    PubMed  Google Scholar 

  134. Zinöcker, M. K. & Lindseth, I. A. The western diet–microbiome–host interaction and its role in metabolic disease. Nutrients 10, 365 (2018).

    PubMed Central  Google Scholar 

  135. Carmody, R. N. et al. Cooking shapes the structure and function of the gut microbiome. Nat. Microbiol. 4, 2052–2063 (2019).

    PubMed  PubMed Central  Google Scholar 

  136. Koppel, N., Rekdal, V. M. & Balskus, E. P. Chemical transformation of xenobiotics by the human gut microbiota. Science 356, eaag2770 (2017).

    PubMed  Google Scholar 

  137. Arcila, J. A. & Rose, D. J. Repeated cooking and freezing of whole wheat flour increases resistant starch with beneficial impacts on in vitro fecal fermentation properties. J. Funct. Foods 12, 230–236 (2015).

    CAS  Google Scholar 

  138. Lerner, A. & Matthias, T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun. Rev. 14, 479–489 (2015).

    CAS  PubMed  Google Scholar 

  139. Obih, C. et al. Specific carbohydrate diet for pediatric inflammatory bowel disease in clinical practice within an academic IBD center. Nutrition 32, 418–425 (2016).

    PubMed  Google Scholar 

  140. Cox, S. R. et al. Effects of low FODMAP diet on symptoms, fecal microbiome, and markers of inflammation in patients with quiescent inflammatory bowel disease in a randomized trial. Gastroenterology 158, 176–188.e7 (2020).

    CAS  PubMed  Google Scholar 

  141. Chassaing, B. et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519, 92–96 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Stephen, A. M. et al. Dietary fibre in Europe: current state of knowledge on definitions, sources, recommendations, intakes and relationships to health. Nutr. Res. Rev. 30, 149–190 (2017).

    CAS  PubMed  Google Scholar 

  143. Logan, M. et al. Analysis of 61 exclusive enteral nutrition formulas used in the management of active Crohn’s disease — new insights into dietary disease triggers. Aliment. Pharmacol. Ther. 51, 935–947 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Brüssow, H. Problems with the concept of gut microbiota dysbiosis. Microb. Biotechnol. 13, 423–434 (2020).

    PubMed  Google Scholar 

  145. Volkova, A. & Ruggles, K. V. Predictive metagenomic analysis of autoimmune disease identifies robust autoimmunity and disease specific microbial signatures. Front. Microbiol. 12, 621310 (2021).

    PubMed  PubMed Central  Google Scholar 

  146. Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).

    CAS  PubMed  Google Scholar 

  147. Zmora, N. et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 174, 1388–1405.e21 (2018).

    CAS  PubMed  Google Scholar 

  148. Korem, T. et al. Bread affects clinical parameters and induces gut microbiome-associated personal glycemic responses. Cell Metab. 25, 1243–1253.e5 (2017).

    CAS  PubMed  Google Scholar 

  149. The Adaptive Platform Trials Coalition Adaptive platform trials: definition, design, conduct and reporting considerations. Nat. Rev. Drug Discov. 18, 797–807 (2019).

    Google Scholar 

  150. Holzinger, D., Kessel, C., Omenetti, A. & Gattorno, M. From bench to bedside and back again: translational research in autoinflammation. Nat. Rev. Rheumatol. 11, 573–585 (2015).

    CAS  PubMed  Google Scholar 

  151. Donaldson, G. P., Lee, S. M. & Mazmanian, S. K. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 14, 20–32 (2016).

    CAS  PubMed  Google Scholar 

  152. Wei, Y. et al. Pectin enhances the effect of fecal microbiota transplantation in ulcerative colitis by delaying the loss of diversity of gut flora. BMC Microbiol. 16, 255 (2016).

    PubMed  PubMed Central  Google Scholar 

  153. Kearney, S. M., Gibbons, S. M., Erdman, S. E. & Alm, E. J. Orthogonal dietary niche enables reversible engraftment of a gut bacterial commensal. Cell Rep. 24, 1842–1851 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Quraishi, M. N. et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment. Pharmacol. Ther. 46, 479–493 (2017).

    CAS  PubMed  Google Scholar 

  156. de Groot, P. et al. Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial. Gut 70, 92–105 (2021).

    PubMed  Google Scholar 

  157. Engen, P. A. et al. Single-arm, non-randomized, time series, single-subject study of fecal microbiota transplantation in multiple sclerosis. Front. Neurol. 11, 978 (2020).

    PubMed  PubMed Central  Google Scholar 

  158. Van Beurden, Y. H. et al. Serendipity in refractory celiac disease: full recovery of duodenal villi and clinical symptoms after fecal microbiota transfer. J. Gastrointest. Liver Dis. 25, 385–388 (2016).

    Google Scholar 

  159. Zeng, J. et al. Fecal microbiota transplantation for rheumatoid arthritis: a case report. Clin. Case Rep. 9, 906–909 (2021).

    PubMed  Google Scholar 

  160. Costello, S. P. et al. Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial. JAMA 321, 156–164 (2019).

    PubMed  PubMed Central  Google Scholar 

  161. Moayyedi, P. et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109.e6 (2015).

    PubMed  Google Scholar 

  162. Paramsothy, S. et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 389, 1218–1228 (2017).

    PubMed  Google Scholar 

  163. Rossen, N. G. et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149, 110–118.e4 (2015).

    PubMed  Google Scholar 

  164. Vaughn, B. P. et al. Increased intestinal microbial diversity following fecal microbiota transplant for active Crohn’s disease. Inflamm. Bowel Dis. 22, 2182–2190 (2016).

    PubMed  Google Scholar 

  165. Cui, B. et al. Fecal microbiota transplantation through mid-gut for refractory Crohn’s disease: safety, feasibility, and efficacy trial results. J. Gastroenterol. Hepatol. 30, 51–58 (2015).

    CAS  PubMed  Google Scholar 

  166. Philips, C. A. et al. Healthy donor fecal microbiota transplantation in steroid-ineligible severe alcoholic hepatitis: a pilot study. Clin. Gastroenterol. Hepatol. 15, 600–602 (2017).

    PubMed  Google Scholar 

  167. Mullish, B. H., McDonald, J. A. K., Thursz, M. R. & Marchesi, J. R. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatol 66, 1354–1355 (2017).

    Google Scholar 

  168. Kootte, R. S. et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 26, 611–619.e6 (2017).

    CAS  PubMed  Google Scholar 

  169. Kang, D. W. et al. Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota. Sci. Rep. 9, 5821 (2019).

    PubMed  PubMed Central  Google Scholar 

  170. Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Dailey, F. E., Turse, E. P., Daglilar, E. & Tahan, V. The dirty aspects of fecal microbiota transplantation: a review of its adverse effects and complications. Curr. Opin. Pharmacol. 49, 29–33 (2019).

    CAS  PubMed  Google Scholar 

  172. Wilson, B. C., Vatanen, T., Cutfield, W. S. & O’Sullivan, J. M. The super-donor phenomenon in fecal microbiota transplantation. Front. Cell. Infect. Microbiol. 9, 2 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Knox, N. C., Forbes, J. D., Van Domselaar, G. & Bernstein, C. N. The gut microbiome as a target for IBD treatment: are we there yet? Curr. Treat. Options Gastroenterol. 17, 115–126 (2019).

    PubMed  Google Scholar 

  174. Burrello, C. et al. Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells. Nat. Commun. 9, 5184 (2018).

    PubMed  PubMed Central  Google Scholar 

  175. Jang, Y. O. et al. Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis. Exp. Mol. Med. 52, 1128–1139 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Anhê, F. F. et al. Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice. Gut 68, 453–464 (2019).

    PubMed  Google Scholar 

  177. Petrof, E. O. et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome 1, 3 (2013).

    PubMed  PubMed Central  Google Scholar 

  178. Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565, 600–605 (2019).

    CAS  PubMed  Google Scholar 

  179. Sood, A. et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin. Gastroenterol. Hepatol. 7, 1202–1209 (2009).

    PubMed  Google Scholar 

  180. Derwa, Y., Gracie, D. J., Hamlin, P. J. & Ford, A. C. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. Aliment. Pharmacol. Ther. 46, 389–400 (2017).

    CAS  PubMed  Google Scholar 

  181. Ganji-Arjenaki, M. & Rafieian-Kopaei, M. Probiotics are a good choice in remission of inflammatory bowel diseases: a meta analysis and systematic review. J. Cell. Physiol. 233, 2091–2103 (2018).

    CAS  PubMed  Google Scholar 

  182. Shigemori, S. & Shimosato, T. Applications of genetically modified immunobiotics with high immunoregulatory capacity for treatment of inflammatory bowel diseases. Front. Immunol. 8, 22 (2017).

    PubMed  PubMed Central  Google Scholar 

  183. Sales-Campos, H., Soares, S. C. & Oliveira, C. J. F. An introduction of the role of probiotics in human infections and autoimmune diseases. Crit. Rev. Microbiol. 45, 413–432 (2019).

    PubMed  Google Scholar 

  184. Flach, J., van der Waal, M. B., van den Nieuwboer, M., Claassen, E. & Larsen, O. F. A. The underexposed role of food matrices in probiotic products: reviewing the relationship between carrier matrices and product parameters. Crit. Rev. Food Sci. Nutr. 58, 2570–2584 (2018).

    CAS  PubMed  Google Scholar 

  185. Cassani, L., Gomez-Zavaglia, A. & Simal-Gandara, J. Technological strategies ensuring the safe arrival of beneficial microorganisms to the gut: from food processing and storage to their passage through the gastrointestinal tract. Food Res. Int. 129, 108852 (2020).

    CAS  PubMed  Google Scholar 

  186. Bezkorovainy, A. Probiotics: determinants of survival and growth in the gut. Am. J. Clin. Nutr. 73 (Suppl. 2), 399–405 (2001).

    Google Scholar 

  187. Maldonado-Gómez, M. X. et al. Stable engraftment of Bifidobacterium longum AH1206 in the human gut depends on individualized features of the resident microbiome. Cell Host Microbe 20, 515–526 (2016).

    PubMed  Google Scholar 

  188. Suez, J. et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell 174, 1406–1423.e16 (2018).

    CAS  PubMed  Google Scholar 

  189. Sorbara, M. T. & Pamer, E. G. Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them. Mucosal Immunol. 12, 1–9 (2019).

    CAS  PubMed  Google Scholar 

  190. Champagne, C. P., Gardner, N. J. & Roy, D. Challenges in the addition of probiotic cultures to foods. Crit. Rev. Food Sci. Nutr. 45, 61–84 (2005).

    CAS  PubMed  Google Scholar 

  191. Fujimori, S. et al. A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis. Nutrition 25, 520–525 (2009).

    PubMed  Google Scholar 

  192. Amiriani, T. et al. Effect of Lactocare® synbiotic on disease severity in ulcerative colitis: a randomized placebo-controlled double-blind clinical trial. Middle East. J. Dig. Dis. 12, 27–33 (2020).

    PubMed  PubMed Central  Google Scholar 

  193. Furrie, E. et al. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54, 242–249 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Steed, H. et al. Clinical trial: the microbiological and immunological effects of synbiotic consumption - a randomized double-blind placebo-controlled study in active Crohn’s disease. Aliment. Pharmacol. Ther. 32, 872–883 (2010).

    CAS  PubMed  Google Scholar 

  195. Zamani, B., Farshbaf, S., Golkar, H. R., Bahmani, F. & Asemi, Z. Synbiotic supplementation and the effects on clinical and metabolic responses in patients with rheumatoid arthritis: a randomised, double-blind, placebo-controlled trial. Br. J. Nutr. 117, 1095–1102 (2017).

    CAS  PubMed  Google Scholar 

  196. Zare Javid, A., Aminzadeh, M., Haghighi-Zadeh, M. H. & Jamalvandi, M. The effects of synbiotic supplementation on glycemic status, lipid profile, and biomarkers of oxidative stress in type 1 diabetic patients. A placebo-controlled, double-blind, randomized clinical trial. Diabetes Metab. Syndr. Obes. 13, 607–617 (2020).

    PubMed  PubMed Central  Google Scholar 

  197. Chen, L., Yang, T., Song, Y., Shu, G. & Chen, H. Effect of xanthan-chitosan-xanthan double layer encapsulation on survival of Bifidobacterium BB01 in simulated gastrointestinal conditions, bile salt solution and yogurt. LWT Food Sci. Technol. 81, 274–280 (2017).

    CAS  Google Scholar 

  198. Fratianni, F. et al. Ability of synbiotic encapsulated Saccharomyces cerevisiae boulardii to grow in berry juice and to survive under simulated gastrointestinal conditions. J. Microencapsul. 31, 299–305 (2014).

    CAS  PubMed  Google Scholar 

  199. Cook, M. T., Tzortzis, G., Charalampopoulos, D. & Khutoryanskiy, V. V. Microencapsulation of a synbiotic into PLGA/alginate multiparticulate gels. Int. J. Pharm. 466, 400–408 (2014).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  201. Pudlo, N. A. et al. Extensive transfer of genes for edible seaweed digestion from marine to human gut bacteria. Preprint at bioRxiv https://doi.org/10.1101/2020.06.09.142968 (2020).

    Article  Google Scholar 

  202. Walter, J., Britton, R. A. & Roos, S. Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc. Natl Acad. Sci. USA 108, 4645–4652 (2011).

    CAS  PubMed  Google Scholar 

  203. Martínez, I. et al. The gut microbiota of rural Papua New Guineans: composition, diversity patterns, and ecological processes. Cell Rep. 11, 527–538 (2015).

    PubMed  Google Scholar 

  204. Mu, Q. et al. Control of lupus nephritis by changes of gut microbiota. Microbiome 5, 73 (2017).

    PubMed  PubMed Central  Google Scholar 

  205. He, B. et al. Lactobacillus reuteri reduces the severity of experimental autoimmune encephalomyelitis in mice by modulating gut microbiota. Front. Immunol. 10, 385 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  206. De Moreno De Leblanc, A. et al. Evaluation of the biosafety of recombinant lactic acid bacteria designed to prevent and treat colitis. J. Med. Microbiol. 65, 1038–1046 (2016).

    PubMed  Google Scholar 

  207. Zeng, L. et al. An engineering probiotic producing defensin-5 ameliorating dextran sodium sulfate-induced mice colitis via Inhibiting NF-κB pathway. J. Transl. Med. 18, 107 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  208. Lerner, A., Matthias, T. & Aminov, R. Potential effects of horizontal gene exchange in the human gut. Front. Immunol. 8, 1630 (2017).

    PubMed  PubMed Central  Google Scholar 

  209. Reynolds, A. et al. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Lancet 393, 434–445 (2019).

    CAS  PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  211. Kjeldsen-Kragh, J. et al. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet 338, 899–902 (1991).

    CAS  PubMed  Google Scholar 

  212. Stoll, M. L. Genetics, Prevotella, and the pathogenesis of rheumatoid arthritis. Lancet Rheumatol. 2, e375–e376 (2020).

    Google Scholar 

  213. Peltonen, R. et al. Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet. Br. J. Rheumatol. 36, 64–68 (1997).

    CAS  PubMed  Google Scholar 

  214. Charbonneau, M. R., Isabella, V. M., Li, N. & Kurtz, C. B. Developing a new class of engineered live bacterial therapeutics to treat human diseases. Nat. Commun. 11, 1738 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  215. FitzGerald, M. J. & Spek, E. J. Microbiome therapeutics and patent protection. Nat. Biotechnol. 38, 806–810 (2020).

    CAS  PubMed  Google Scholar 

  216. Lloyd-Price, J., Abu-Ali, G. & Huttenhower, C. The healthy human microbiome. Genome Med. 8, 51 (2016).

    PubMed  PubMed Central  Google Scholar 

  217. Schellekens, H. et al. Bifidobacterium longum counters the effects of obesity: partial successful translation from rodent to human. EBioMedicine 63, 103176 (2021).

    CAS  PubMed  Google Scholar 

  218. Fragiadakis, G. K. et al. Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight. Am. J. Clin. Nutr. 111, 1127–1136 (2020).

    PubMed  PubMed Central  Google Scholar 

  219. Genoni, A. et al. Long-term Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentrations. Eur. J. Nutr. 59, 1845–1848 (2020).

    CAS  PubMed  Google Scholar 

  220. Saresella, M. et al. Immunological and clinical effect of diet modulation of the gut microbiome in multiple sclerosis patients: a pilot study. Front. Immunol. 8, 1391 (2017).

    PubMed  PubMed Central  Google Scholar 

  221. Laffin, M. et al. A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice. Sci. Rep. 9, 12294 (2019).

    PubMed  PubMed Central  Google Scholar 

  222. Rodriguez-Palacios, A. et al. The artificial sweetener Splenda promotes gut proteobacteria, dysbiosis, and myeloperoxidase reactivity in Crohn’s disease-like ileitis. Inflamm. Bowel Dis. 24, 1005–1020 (2018).

    PubMed  PubMed Central  Google Scholar 

  223. Grabinger, T. et al. Alleviation of intestinal inflammation by oral supplementation with 2-fucosyllactose in mice. Front. Microbiol. 10, 1385 (2019).

    PubMed  PubMed Central  Google Scholar 

  224. Berer, K. et al. Dietary non-fermentable fiber prevents autoimmune neurological disease by changing gut metabolic and immune status. Sci. Rep. 8, 10431 (2018).

    PubMed  PubMed Central  Google Scholar 

  225. Chen, K. et al. Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis. Mol. Nutr. Food Res. 61, 1601006 (2017).

    Google Scholar 

  226. Gudi, R. et al. Complex dietary polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes. Immunology 157, 70–85 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  227. Rosser, E. C. et al. Microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells. Cell Metab. 31, 837–851.e10 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  228. Zhang, T. et al. Sodium butyrate reduces colitogenic immunoglobulin A-coated bacteria and modifies the composition of microbiota in IL-10 deficient mice. Nutrients 8, 728 (2016).

    PubMed Central  Google Scholar 

  229. Choi, S. C. et al. Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice. Sci. Transl. Med. 12, eaax2220 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  230. Alrafas, H. R., Busbee, P. B., Nagarkatti, M. & Nagarkatti, P. S. Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells. J. Leukoc. Biol. 106, 467–480 (2019).

    CAS  PubMed  Google Scholar 

  231. Constante, M., Fragoso, G., Calvé, A., Samba-Mondonga, M. & Santos, M. M. Dietary heme induces gut dysbiosis, aggravates colitis, and potentiates the development of adenomas in mice. Front. Microbiol. 8, 1809 (2017).

    PubMed  PubMed Central  Google Scholar 

  232. Lee, T. et al. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 66, 863–871 (2016).

    PubMed  Google Scholar 

  233. Miranda, P. M. et al. High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production. Microbiome 6, 57 (2018).

    PubMed  PubMed Central  Google Scholar 

  234. Wilck, N. et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 551, 585–589 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  235. Eaton, S. B. & Konner, M. Paleolithic nutrition: a consideration of its nature and current implications. N. Engl. J. Med. 312, 283–289 (1985).

    CAS  PubMed  Google Scholar 

  236. Cordain, L. et al. Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets. Am. J. Clin. Nutr. 71, 682–692 (2000).

    CAS  PubMed  Google Scholar 

  237. Diamond, J. Evolution, consequences and future of plant and animal domestication. Nature 418, 700–707 (2002).

    CAS  PubMed  Google Scholar 

  238. Burkitt, D. Related disease — related cause? Lancet 294, 1229–1231 (1969).

    Google Scholar 

  239. Burkitt, D. P., Walker, A. R. P. & Painter, N. S. Dietary fiber and disease. JAMA 229, 1068–1074 (1974).

    CAS  PubMed  Google Scholar 

  240. Aries, V., Crowther, J. S., Drasar, B. S., Hill, M. J. & Williams, R. E. Bacteria and the aetiology of cancer of the large bowel. Gut 10, 334–335 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  241. Gu, P. & Feagins, L. A. Dining with inflammatory bowel disease: a review of the literature on diet in the pathogenesis and management of IBD. Inflamm. Bowel Dis. 26, 181–191 (2020).

    PubMed  Google Scholar 

  242. Sabino, J., Lewis, J. D. & Colombel, J. F. Treating inflammatory bowel disease with diet: a taste test. Gastroenterology 157, 295–297 (2019).

    PubMed  Google Scholar 

  243. Hou, J. K., Lee, D. & Lewis, J. Diet and inflammatory bowel disease: review of patient-targeted recommendations. Clin. Gastroenterol. Hepatol. 12, 1592–1600 (2014).

    PubMed  Google Scholar 

  244. Moayyedi, P., Simrén, M. & Bercik, P. Evidence-based and mechanistic insights into exclusion diets for IBS. Nat. Rev. Gastroenterol. Hepatol. 17, 406–413 (2020).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the following grants in the laboratory of M.S.D.: Luxembourg National Research Fund (FNR) CORE grants (C15/BM/10318186 and C18/BM/12585940) to M.S.D.; M.B. was supported by a European Commission Horizon 2020 Marie Skłodowska-Curie Actions individual fellowship (897408); M.W. was supported by a Fulbright grant for Visiting Scholars from the Commission for Educational Exchange between the United States of America, Belgium and Luxembourg; E.T.G. was supported by the Luxembourg National Research Fund PRIDE (17/11823097) and the Fondation du Pélican de Mie et Pierre Hippert-Faber, under the aegis of the Fondation de Luxembourg. G.V.P. was supported by a fellowship from the W. Garfield Weston Foundation and E.C.M. acknowledges the financial support from National Institutes of Health (DK118024).

Author information

Authors and Affiliations

Authors

Contributions

All authors have contributed to the writing and editing of the manuscript.

Corresponding author

Correspondence to Mahesh S. Desai.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Gastroenterology & Hepatology thanks R. Carmody and the other, anonymous, reviewers for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wolter, M., Grant, E.T., Boudaud, M. et al. Leveraging diet to engineer the gut microbiome. Nat Rev Gastroenterol Hepatol 18, 885–902 (2021). https://doi.org/10.1038/s41575-021-00512-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-021-00512-7

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing