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Recipient factors in faecal microbiota transplantation: one stool does not fit all

Nature Reviews Gastroenterology & Hepatology volume 18, pages 503–513 (2021)Cite this article

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Abstract

Faecal microbiota transplantation (FMT) is a promising therapy for chronic diseases associated with gut microbiota alterations. FMT cures 90% of recurrent Clostridioides difficile infections. However, in complex diseases, such as inflammatory bowel disease, irritable bowel syndrome and metabolic syndrome, its efficacy remains variable. It is accepted that donor selection and sample administration are key determinants of FMT success, yet little is known about the recipient factors that affect it. In this Perspective, we discuss the effects of recipient parameters, such as genetics, immunity, microbiota and lifestyle, on donor microbiota engraftment and clinical efficacy. Emerging evidence supports the possibility that controlling inflammation in the recipient intestine might facilitate engraftment by reducing host immune system pressure on the newly transferred microbiota. Deciphering FMT engraftment rules and developing novel therapeutic strategies are priorities to alleviate the burden of chronic diseases associated with an altered gut microbiota such as inflammatory bowel disease.

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Fig. 1: Effects of the host immune system on intestinal microbiota composition and functions.
Fig. 2: Potential targets and strategies on the recipient side to improve FMT efficacy.

References

  1. Eckburg, P. B. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    PubMed  PubMed Central  Google Scholar 

  2. D’Haens, G. R. & Jobin, C. Fecal microbial transplantation for diseases beyond recurrent clostridium difficile infection. Gastroenterology 157, 624–636 (2019).

    PubMed  Google Scholar 

  3. Durack, J. & Lynch, S. V. The gut microbiome: relationships with disease and opportunities for therapy. J. Exp. Med. 216, 20–40 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Vujkovic-Cvijin, I. et al. Host variables confound gut microbiota studies of human disease. Nature 587, 448–454 (2020).

    PubMed  PubMed Central  Google Scholar 

  5. 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 

  6. Galipeau, H. J. et al. Novel fecal biomarkers that precede clinical diagnosis of ulcerative colitis. Gastroenterology https://doi.org/10.1053/j.gastro.2020.12.004 (2020).

    Article  PubMed  Google Scholar 

  7. Britton, G. J. et al. Microbiotas from humans with inflammatory bowel disease alter the balance of gut Th17 and RORγt+ regulatory T cells and exacerbate colitis in mice. Immunity 50, 212–224 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Le Roy, T. et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut 62, 1787–1794 (2013).

    PubMed  Google Scholar 

  9. De Palma, G. et al. Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice. Sci. Transl Med. 9, eaaf6397 (2017).

    PubMed  Google Scholar 

  10. van Nood, E. et al. Duodenal infusion of donor feces for recurrent clostridium difficile. N. Engl. J. Med. 368, 407–415 (2013).

    PubMed  Google Scholar 

  11. Kelly, C. R. et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent clostridium difficile infection: a randomized trial. Ann. Intern. Med. 165, 609 (2016).

    PubMed  PubMed Central  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  14. 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 

  15. 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 (2019).

    PubMed  PubMed Central  Google Scholar 

  16. Sandborn, W. J. et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 146, 85–95 (2014).

    CAS  PubMed  Google Scholar 

  17. Feagan, B. G. et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 369, 699–710 (2013).

    CAS  PubMed  Google Scholar 

  18. Colman, R. J. & Rubin, D. T. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J. Crohns Colitis 8, 1569–1581 (2014).

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  20. Suskind, D. L. et al. Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn’s disease. Inflamm. Bowel Dis. 21, 556–563 (2015).

    PubMed  Google Scholar 

  21. 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 

  22. He, Z. et al. Multiple fresh fecal microbiota transplants induces and maintains clinical remission in Crohn’s disease complicated with inflammatory mass. Sci. Rep. 7, 4753 (2017).

    PubMed  PubMed Central  Google Scholar 

  23. Sokol, H. et al. Fecal microbiota transplantation to maintain remission in Crohn’s disease: a pilot randomized controlled study. Microbiome 8, 12 (2020).

    PubMed  PubMed Central  Google Scholar 

  24. Johnsen, P. H. et al. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol. Hepatol. 3, 17–24 (2018).

    PubMed  Google Scholar 

  25. El-Salhy, M., Hatlebakk, J. G., Gilja, O. H., Bråthen Kristoffersen, A. & Hausken, T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut 69, 859–867 (2020).

    CAS  PubMed  Google Scholar 

  26. Halkjær, S. I. et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study. Gut 67, 2107–2115 (2018).

    PubMed  Google Scholar 

  27. Holster, S. et al. The effect of allogenic versus autologous fecal microbiota transfer on symptoms, visceral perception and fecal and mucosal microbiota in irritable bowel syndrome: a randomized controlled study. Clin. Transl Gastroenterol. 10, e00034 (2019).

    PubMed  PubMed Central  Google Scholar 

  28. Aroniadis, O. C. et al. Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol. Hepatol. 4, 675–685 (2019).

    PubMed  Google Scholar 

  29. Kakihana, K. et al. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood 128, 2083–2088 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Spindelboeck, W. et al. Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute, refractory gastrointestinal graft- versus -host-disease. Haematologica 102, e210–e213 (2017).

    PubMed  PubMed Central  Google Scholar 

  31. Qi, X. et al. Treating steroid refractory intestinal acute graft-vs.-host disease with fecal microbiota transplantation: a pilot study. Front. Immunol. 9, 2195 (2018).

    PubMed  PubMed Central  Google Scholar 

  32. Bajaj, J. S. et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology 66, 1727–1738 (2017).

    CAS  PubMed  Google Scholar 

  33. Bajaj, J. S. et al. Long-term outcomes of fecal microbiota transplantation in patients with cirrhosis. Gastroenterology 156, 1921–1923 (2019).

    PubMed  Google Scholar 

  34. Bajaj, J. S. et al. Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis. JCI Insight 4, e133410 (2019).

    PubMed Central  Google Scholar 

  35. Bajaj, J. S. et al. A randomized clinical trial of fecal microbiota transplant for alcohol use disorder. Hepatology https://doi.org/10.1002/hep.31496 (2020).

    Article  PubMed  Google Scholar 

  36. Vrieze, A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913–916 (2012).

    CAS  PubMed  Google Scholar 

  37. 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 (2017).

    CAS  PubMed  Google Scholar 

  38. Kang, D.-W. et al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 5, 10 (2017).

    PubMed  PubMed Central  Google Scholar 

  39. 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 

  40. Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Couturier-Maillard, A. et al. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J. Clin. Invest. 123, 700–711 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Petnicki-Ocwieja, T. et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc. Natl Acad. Sci. USA 106, 15813–15818 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Hu, B. et al. Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc. Natl Acad. Sci. USA 110, 9862–9867 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 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 

  45. Khan, A. A. et al. Polymorphic immune mechanisms regulate commensal repertoire. Cell Rep. 29, 541–550 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Wen, L. et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455, 1109–1113 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science 328, 228–231 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kawamoto, S. et al. Foxp3+ T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity 41, 152–165 (2014).

    CAS  PubMed  Google Scholar 

  49. Zhang, H., Sparks, J. B., Karyala, S. V., Settlage, R. & Luo, X. M. Host adaptive immunity alters gut microbiota. ISME J. 9, 770–781 (2015).

    CAS  PubMed  Google Scholar 

  50. Dimitriu, P. A. et al. Temporal stability of the mouse gut microbiota in relation to innate and adaptive immunity: mouse gut microbiota dynamics. Environ. Microbiol. Rep. 5, 200–210 (2013).

    CAS  PubMed  Google Scholar 

  51. Sokol, H. et al. Card9 mediates intestinal epithelial cell restitution, T-helper 17 responses, and control of bacterial infection in mice. Gastroenterology 145, 591–601 (2013).

    CAS  PubMed  Google Scholar 

  52. Richard, M. L. & Sokol, H. The gut mycobiota: insights into analysis, environmental interactions and role in gastrointestinal diseases. Nat. Rev. Gastroenterol. Hepatol. 16, 331–345 (2019).

    PubMed  Google Scholar 

  53. Sovran, B. et al. Enterobacteriaceae are essential for the modulation of colitis severity by fungi. Microbiome 6, 152 (2018).

    PubMed  PubMed Central  Google Scholar 

  54. van Tilburg Bernardes, E. et al. Intestinal fungi are causally implicated in microbiome assembly and immune development in mice. Nat. Commun. 11, 2577 (2020).

    PubMed  PubMed Central  Google Scholar 

  55. Turpin, W. et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat. Genet. 48, 1413–1417 (2016).

    CAS  PubMed  Google Scholar 

  56. Bonder, M. J. et al. The effect of host genetics on the gut microbiome. Nat. Genet. 48, 1407–1412 (2016).

    CAS  PubMed  Google Scholar 

  57. Wang, J. et al. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat. Genet. 48, 1396–1406 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Benson, A. K. The gut microbiome-an emerging complex trait. Nat. Genet. 48, 1301–1302 (2016).

    CAS  PubMed  Google Scholar 

  59. Hansen, J. J. Immune responses to intestinal microbes in inflammatory bowel diseases. Curr. Allergy Asthma Rep. 15, 61 (2015).

    PubMed  Google Scholar 

  60. Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15, 382–392 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Morgan, X. C. et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 13, R79 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Chu, H. et al. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science 352, 1116–1120 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Sadaghian Sadabad, M. et al. The ATG16L1–T300A allele impairs clearance of pathosymbionts in the inflamed ileal mucosa of Crohn’s disease patients. Gut 64, 1546–1552 (2015).

    PubMed  Google Scholar 

  64. Frank, D. N. et al. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm. Bowel Dis. 17, 179–184 (2011).

    PubMed  Google Scholar 

  65. Aschard, H. et al. Genetic effects on the commensal microbiota in inflammatory bowel disease patients. PLoS Genet. 15, e1008018 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Sokol, H. et al. Intestinal dysbiosis in inflammatory bowel disease associated with primary immunodeficiency. J. Allergy Clin. Immunol. 143, 775–778 (2019).

    PubMed  Google Scholar 

  67. Raffatellu, M. et al. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe 5, 476–486 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Liu, J. Z. et al. Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host Microbe 11, 227–239 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Deriu, E. et al. Probiotic bacteria reduce Salmonella typhimurium intestinal colonization by competing for iron. Cell Host Microbe 14, 26–37 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Winter, S. E. et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339, 708–711 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Winter, S. E. & Bäumler, A. J. Dysbiosis in the inflamed intestine: chance favors the prepared microbe. Gut Microbes 5, 71–73 (2014).

    PubMed  PubMed Central  Google Scholar 

  72. Faber, F. & Bäumler, A. J. The impact of intestinal inflammation on the nutritional environment of the gut microbiota. Immunol. Lett. 162, 48–53 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Zechner, E. L. Inflammatory disease caused by intestinal pathobionts. Curr. Opin. Microbiol. 35, 64–69 (2017).

    PubMed  Google Scholar 

  74. Bunker, J. J. & Bendelac, A. IgA responses to microbiota. Immunity 49, 211–224 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. van der Waaij, L. A. et al. Immunoglobulin coating of faecal bacteria in inflammatory bowel disease. Eur. J. Gastroenterol. Hepatol. 16, 669–674 (2004).

    PubMed  Google Scholar 

  76. Palm, N. W. et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158, 1000–1010 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Viladomiu, M. et al. IgA-coated E. coli enriched in Crohn’s disease spondyloarthritis promote T H 17-dependent inflammation. Sci. Transl Med. 9, eaaf9655 (2017).

    PubMed  PubMed Central  Google Scholar 

  78. Aghamohammadi, A. et al. IgA deficiency: correlation between clinical and immunological phenotypes. J. Clin. Immunol. 29, 130–136 (2009).

    CAS  PubMed  Google Scholar 

  79. Ludvigsson, J. F., Neovius, M. & Hammarström, L. Association between IgA deficiency & other autoimmune conditions: a population-based matched cohort study. J. Clin. Immunol. 34, 444–451 (2014).

    CAS  PubMed  Google Scholar 

  80. Catanzaro, J. R. et al. IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM. Sci. Rep. 9, 13574 (2019).

    PubMed  PubMed Central  Google Scholar 

  81. Mirpuri, J. et al. Proteobacteria-specific IgA regulates maturation of the intestinal microbiota. Gut Microbes 5, 28–39 (2014).

    PubMed  Google Scholar 

  82. Suzuki, K. et al. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc. Natl Acad. Sci. USA 101, 1981–1986 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Harriman, G. R. et al. Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes. J. Immunol. 162, 2521–2529 (1999).

    CAS  PubMed  Google Scholar 

  84. Macpherson, A. J. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288, 2222–2226 (2000).

    CAS  PubMed  Google Scholar 

  85. Kubinak, J. L. et al. MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health. Cell Host Microbe 17, 153–163 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Kubinak, J. L. et al. MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection. Nat. Commun. 6, 8642 (2015).

    CAS  PubMed  Google Scholar 

  87. Nakajima, A. et al. IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria. J. Exp. Med. 215, 2019–2034 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Zuo, T. et al. Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection. Nat. Commun. 9, 3663 (2018).

    PubMed  PubMed Central  Google Scholar 

  89. Vermeire, S. et al. Donor species richness determines faecal microbiota transplantation success in inflammatory bowel disease. J. Crohns Colitis 10, 387–394 (2016).

    PubMed  Google Scholar 

  90. Paramsothy, S. et al. Specific bacteria and metabolites associated with response to fecal microbiota transplantation in patients with ulcerative colitis. Gastroenterology 156, 1440–1454 (2019).

    PubMed  Google Scholar 

  91. Lavelle, A. & Sokol, H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 17, 223–237 (2020).

    PubMed  Google Scholar 

  92. McCarville, J. L., Chen, G. Y., Cuevas, V. D., Troha, K. & Ayres, J. S. Microbiota metabolites in health and disease. Annu. Rev. Immunol. 38, 147–170 (2020).

    CAS  PubMed  Google Scholar 

  93. Weingarden, A. R. et al. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am. J. Physiol. Gastrointest. Liver Physiol. 306, G310–G319 (2014).

    CAS  PubMed  Google Scholar 

  94. Buffie, C. G. et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208 (2015).

    CAS  PubMed  Google Scholar 

  95. Staley, C., Kelly, C. R., Brandt, L. J., Khoruts, A. & Sadowsky, M. J. Complete microbiota engraftment is not essential for recovery from recurrent clostridium difficile infection following fecal microbiota transplantation. mBio 7, e01965–16 (2016).

    PubMed  PubMed Central  Google Scholar 

  96. Seekatz, A. M. et al. Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection. Anaerobe 53, 64–73 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Brown, J. R.-M. et al. Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infection. BMC Gastroenterol. 18, 131 (2018).

    PubMed  PubMed Central  Google Scholar 

  98. Mullish, B. H. et al. Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection. Gut 68, 1791–1800 (2019).

    CAS  PubMed  Google Scholar 

  99. Winston, J. A. et al. Ursodeoxycholic acid (UDCA) mitigates the host inflammatory response during Clostridioides difficile infection by altering gut bile acids. Infect. Immun. 88, e00045-20 (2020).

    PubMed  PubMed Central  Google Scholar 

  100. Monaghan, T. et al. Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway. Gut Microbes 10, 142–148 (2019).

    CAS  PubMed  Google Scholar 

  101. Gadaleta, R. M. et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut 60, 463–472 (2011).

    CAS  PubMed  Google Scholar 

  102. Wilson, A., Almousa, A., Teft, W. A. & Kim, R. B. Attenuation of bile acid-mediated FXR and PXR activation in patients with Crohn’s disease. Sci. Rep. 10, 1866 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. McDonald, J. A. K. et al. Inhibiting growth of clostridioides difficile by restoring valerate, produced by the intestinal microbiota. Gastroenterology 155, 1495–1507 (2018).

    CAS  PubMed  Google Scholar 

  104. Ott, S. J. et al. Efficacy of sterile fecal filtrate transfer for treating patients with clostridium difficile infection. Gastroenterology 152, 799–811 (2017).

    PubMed  Google Scholar 

  105. Zuo, T. et al. Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome. Gut 67, 634–643 (2017).

    PubMed  Google Scholar 

  106. Broecker, F. et al. Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation. Mol. Case Studies 2, a000448 (2016).

    Google Scholar 

  107. Staley, C. et al. Durable long-term bacterial engraftment following encapsulated fecal microbiota transplantation to treat clostridium difficile infection. mBio 10, e01586-19 (2019).

    PubMed  PubMed Central  Google Scholar 

  108. Goloshchapov, O. V. et al. Long-term impact of fecal transplantation in healthy volunteers. BMC Microbiol. 19, 312 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Moss, E. L. et al. Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients. PLoS ONE 12, e0182585 (2017).

    PubMed  PubMed Central  Google Scholar 

  110. Craven, L. et al. Allogenic fecal microbiota transplantation in patients with nonalcoholic fatty liver disease improves abnormal small intestinal permeability: a randomized control trial. Am. J. Gastroenterol. 115, 1055–1065 (2020).

    PubMed  Google Scholar 

  111. Pigneur, B. & Sokol, H. Fecal microbiota transplantation in inflammatory bowel disease: the quest for the holy grail. Mucosal Immunol. 9, 1360–1365 (2016).

    CAS  PubMed  Google Scholar 

  112. Kim, K. O. & Gluck, M. Fecal microbiota transplantation: an update on clinical practice. Clin. Endosc. 52, 137–143 (2019).

    PubMed  PubMed Central  Google Scholar 

  113. Allegretti, J. R., Mullish, B. H., Kelly, C. & Fischer, M. The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications. Lancet 394, 420–431 (2019).

    CAS  PubMed  Google Scholar 

  114. 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 

  115. Kump, P. et al. The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis. Aliment. Pharmacol. Ther. 47, 67–77 (2018).

    CAS  PubMed  Google Scholar 

  116. Park, H. et al. The success of fecal microbial transplantation in Clostridium difficile infection correlates with bacteriophage relative abundance in the donor: a retrospective cohort study. Gut Microbes 10, 676–687 (2019).

    PubMed  PubMed Central  Google Scholar 

  117. Fuentes, S. et al. Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation. ISME J. 11, 1877–1889 (2017).

    PubMed  PubMed Central  Google Scholar 

  118. Basson, A. R., Zhou, Y., Seo, B., Rodriguez-Palacios, A. & Cominelli, F. Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease. Transl Res. 226, 1–11 (2020).

    PubMed  PubMed Central  Google Scholar 

  119. Rinott, E. et al. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain. Gastroenterology 160, 158–173 (2020).

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  121. Li, S. S. et al. Durable coexistence of donor and recipient strains after fecal microbiota transplantation. Science 352, 586–589 (2016).

    CAS  PubMed  Google Scholar 

  122. Fischer, M. et al. Predictors of early failure after fecal microbiota transplantation for the therapy of clostridium difficile infection: a multicenter study. Am. J. Gastroenterol. 111, 1024–1031 (2016).

    PubMed  Google Scholar 

  123. Gallo, A. et al. Fecal calprotectin and need of multiple microbiota trasplantation infusions in Clostridium difficile infection. J. Gastroenterol. Hepatol. 35, 1909–1915 (2020).

    CAS  PubMed  Google Scholar 

  124. Hirten, R. P. et al. Microbial engraftment and efficacy of fecal microbiota transplant for clostridium difficile in patients with and without inflammatory bowel disease. Inflamm. Bowel Dis. 25, 969–979 (2019).

    PubMed  PubMed Central  Google Scholar 

  125. Ponce-Alonso, M. et al. P782 A new compatibility test for donor selection for faecal microbiota transplantation in ulcerative colitis. J. Crohns Colitis 11 (Suppl. 1), S480–S481 (2017).

    Google Scholar 

  126. Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623–628 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Mullish, B. H. et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut 67, 1920–1941 (2018).

    PubMed  Google Scholar 

  128. Imhann, F. et al. Proton pump inhibitors affect the gut microbiome. Gut 65, 740–748 (2016).

    CAS  PubMed  Google Scholar 

  129. Hong, A. S. et al. Proton pump inhibitor in upper gastrointestinal fecal microbiota transplant: a systematic review and analysis. J. Gastroenterol. Hepatol. 35, 932–940 (2020).

    PubMed  Google Scholar 

  130. Smillie, C. S. et al. Strain tracking reveals the determinants of bacterial engraftment in the human gut following fecal microbiota transplantation. Cell Host Microbe 23, 229–240 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Holvoet, T. et al. Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating. Gut 66, 980–982 (2017).

    PubMed  Google Scholar 

  132. Leonardi, I. et al. Fungal trans-kingdom dynamics linked to responsiveness to fecal microbiota transplantation (FMT) therapy in ulcerative colitis. Cell Host Microbe 27, 823–829 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Gogokhia, L. et al. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. Cell Host Microbe 25, 285–299 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Conceição-Neto, N. et al. Low eukaryotic viral richness is associated with faecal microbiota transplantation success in patients with UC. Gut 67, 1558–1559 (2018).

    PubMed  Google Scholar 

  135. Ianiro, G. et al. Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study. Clin. Microbiol. Infect. 23, 337.e1–337.e3 (2017).

    CAS  Google Scholar 

  136. Sokol, H. Antibiotics: a trigger for inflammatory bowel disease? Lancet Gastroenterol. Hepatol. 5, 956–957 (2020).

    PubMed  Google Scholar 

  137. Keshteli, A. H., Millan, B. & Madsen, K. L. Pretreatment with antibiotics may enhance the efficacy of fecal microbiota transplantation in ulcerative colitis: a meta-analysis. Mucosal Immunol. 10, 565–566 (2017).

    CAS  PubMed  Google Scholar 

  138. Ishikawa, D. et al. Changes in intestinal microbiota following combination therapy with fecal microbial transplantation and antibiotics for ulcerative colitis. Inflamm. Bowel Dis. 23, 116–125 (2017).

    PubMed  Google Scholar 

  139. Le Roy, T. et al. Comparative evaluation of microbiota engraftment following fecal microbiota transfer in mice models: age, kinetic and microbial status matter. Front. Microbiol. 9, 3289 (2019).

    PubMed  PubMed Central  Google Scholar 

  140. Ji, S. K. et al. Preparing the gut with antibiotics enhances gut microbiota reprogramming efficiency by promoting xenomicrobiota colonization. Front. Microbiol. 8, 1208 (2017).

    PubMed  PubMed Central  Google Scholar 

  141. Freitag, T. L. et al. Minor effect of antibiotic pre-treatment on the engraftment of donor microbiota in fecal transplantation in mice. Front. Microbiol. 10, 2685 (2019).

    PubMed  PubMed Central  Google Scholar 

  142. Tian, C. et al. Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections. Nat. Commun. 8, 599 (2017).

    PubMed  PubMed Central  Google Scholar 

  143. Andeweg, S. P., Keşmir, C. & Dutilh, B. E. Quantifying the impact of human leukocyte antigen on the human gut microbiome. bioRxiv https://doi.org/10.1101/2020.01.14.907196 (2020).

    Article  Google Scholar 

  144. 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 (2019).

    PubMed  Google Scholar 

  145. Svolos, V. et al. Treatment of active Crohn’s disease with an ordinary food-based diet that replicates exclusive enteral nutrition. Gastroenterology 156, 1354–1367 (2019).

    PubMed  Google Scholar 

  146. 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 

  147. Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013).

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  149. Augustyn, M., Grys, I. & Kukla, M. Small intestinal bacterial overgrowth and nonalcoholic fatty liver disease. Clin. Exp. Hepatol. 5, 1–10 (2019).

    PubMed  PubMed Central  Google Scholar 

  150. Kastl, A. J., Terry, N. A., Wu, G. D. & Albenberg, L. G. The structure and function of the human small intestinal microbiota: current understanding and future directions. Cell. Mol. Gastroenterol. Hepatol. 9, 33–45 (2020).

    PubMed  Google Scholar 

  151. Knights, D. et al. Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med. 6, 107 (2014).

    PubMed  PubMed Central  Google Scholar 

  152. Mizuno, S. et al. Bifidobacterium-rich fecal donor may be a positive predictor for successful fecal microbiota transplantation in patients with irritable bowel syndrome. Digestion 96, 29–38 (2017).

    PubMed  Google Scholar 

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Acknowledgements

H.S. received funding from Agence National de Recherche (ANR-17-CE15–0019–01). N.R. and H.S. received support from the AFA (Association François Aupetit).

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Authors and Affiliations

  1. INRA, UMR1319 Micalis & AgroParisTech, Jouy en Josas, France

    Camille Danne & Harry Sokol

  2. Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France

    Camille Danne, Nathalie Rolhion & Harry Sokol

  3. Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, Paris, France

    Camille Danne, Nathalie Rolhion & Harry Sokol

  4. French Group of Fecal Microbiota Transplantation (GFTF), Paris, France

    Nathalie Rolhion & Harry Sokol

  5. AP-HP Fecal Microbiota transplantation Center, Saint Antoine Hospital, Paris, France

    Harry Sokol

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  1. Camille Danne
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  3. Harry Sokol
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Contributions

C.D. researched data for the article, made a substantial contribution to the discussion of content, wrote the article and reviewed/edited the manuscript before submission. H.S. and N.R. researched data for the article, made a substantial contribution to the discussion of content and reviewed/edited the manuscript before submission.

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Correspondence to Harry Sokol.

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Competing interests

H.S. received unrestricted study grants from Danone, Biocodex, and Enterome, board membership, consultancy or lecture fees from Carenity, Abbvie, Astellas, Danone, Ferring, Mayoly Spindler, MSD, Novartis, Roche, Tillots, Enterome, Maat, BiomX, Biose, Novartis and Takeda, and is a co-founder of Exeliom bioscience. The other authors declare no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks G. Cammarota, B. Mullish and K. Madsen for their contribution to the peer review of this work.

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Danne, C., Rolhion, N. & Sokol, H. Recipient factors in faecal microbiota transplantation: one stool does not fit all. Nat Rev Gastroenterol Hepatol 18, 503–513 (2021). https://doi.org/10.1038/s41575-021-00441-5

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