Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes?
Purpose of Review
The aim of this review is to summarize the current data available on the metabolic effects of fecal microbiota transplantation (FMT) including obesity and glucose metabolism in humans.
Gut microbiota dysbiosis is a frequent characteristic observed in obesity and related metabolic diseases. Pieces of evidence mostly generated in mouse models suggest that rescuing this dysbiosis associates with improved metabolism. In humans, dietary or bariatric surgery interventions are often accompanied by complete or partial restoration of this dysbiosis together with weight reduction and metabolic amelioration. FMT is an interesting option to modify gut microbiota and has been associated with improved clinical outcomes, albeit only used in routine care for Clostridium difficile infection. However, there are only limited data on using FMT in the metabolic context.
FMT from lean donors significantly improves insulin sensitivity in obese subjects with metabolic syndrome. However, there is a wide range of clinical responses. Interestingly in subjects with high microbial gene richness at baseline and when FMT donors that are metabolically compromised are used, no metabolic improvement is seen. Moreover, more studies evaluating the effect of FMT in patients with overt type 2 diabetes are warranted. Furthermore, interventions (in the receiver prior to FMT) aiming to enhance FMT response also need evaluation.
KeywordsMicrobiota Obesity Type 2 diabetes Fecal microbiota transplantation Encapsulated feces
Grant supports in this field were obtained by Ministry of Health and Solidarity (Assistance Publique-Hôpitaux de Paris: to JAW/PHRC-N Drifter, to KC/PHRC Micronaria), by European Union (Metacardis to KC HEALTH-F4-2012-305312, JPI MICRODIET Grant (5290510105) to KC and MN, EU Horizon 2020 grant (LITMUS 777377) to KC and MN) and by LeDucq Foundation consortium grant (17CVD01) to KC and MN. MN is also supported by a ZONMW-VIDI grant 2013 (016.146.327). JAW and KC are part of ICAN (Institute of Cardiometabolism and Nutrition Institute).
Compliance with Ethical Standards
Conflict of Interest
Judith Aron-Wisnewsky declares that she has no conflict of interest.
Karine Clément is on the Scientific Advisory Board of LNC Therapeutics, France.
Max Nieuwdorp is on the Scientific Advisory Board of Caelus Pharmaceuticals, the Netherlands.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 9.•• Aron-Wisnewsky J, Prifti E, Belda E, Ichou F, Kayser BD, Dao MC, et al. Major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut. 2018 Jun 13. This study demonstrates that severe obesity is associated with a dramatic increased prevalence of low MGR. Bariatric surgery is able to partially restore gut microbiota dysbiosis. Google Scholar
- 13.Debédat J, Amouyal C, Aron-Wisnewsky J, Clément K. Impact of bariatric surgery on type 2 diabetes: contribution of inflammation and gut microbiome? Semin Immunopathol. 2019;Google Scholar
- 17.Koutnikova H, Genser B, Monteiro-Sepulveda M, Faurie J-M, Rizkalla S, Schrezenmeir J, et al. Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2019;9(3):e017995.PubMedPubMedCentralCrossRefGoogle Scholar
- 19.Tremaroli V, Karlsson F, Werling M, Ståhlman M, Kovatcheva-Datchary P, Olbers T, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22(2):228–38.PubMedPubMedCentralCrossRefGoogle Scholar
- 26.•• van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15. This RCT is the first to demonstrate the efficacy of FMT to cure Clostridium difficile infection.PubMedCrossRefGoogle Scholar
- 27.•• Youngster I, Sauk J, Pindar C, Wilson RG, Kaplan JL, Smith MB, et al. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis Off Publ Infect Dis Soc Am. 2014;58(11):1515–22. This study demonstrated for the first time the efficacy of capsulized oral fecal microbiota transplantation.CrossRefGoogle Scholar
- 30.Quraishi MN, Widlak M, Bhala N, Moore D, Price M, Sharma 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. 2017;46(5):479–93.PubMedCrossRefGoogle Scholar
- 32.Debast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2014;20(Suppl 2):1–26.Google Scholar
- 33.McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis Off Publ Infect Dis Soc Am. 2018;66(7):987–94.CrossRefGoogle Scholar
- 42.van Beurden YH, de Groot PF, van Nood E, Nieuwdorp M, Keller JJ, Goorhuis A. Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection. United Eur Gastroenterol J. 2017;5(6):868–79.CrossRefGoogle Scholar
- 49.Cheminet G, Kapel N, Bleibtreu A, Sadou-Yaye H, Bellanger A, Duval X, et al. Faecal microbiota transplantation with frozen capsules for relapsing Clostridium difficile infections: the first experience from 15 consecutive patients in France. J Hosp Infect. 2018.Google Scholar
- 53.•• Kootte RS, Levin E, Salojärvi J, Smits LP, Hartstra AV, Udayappan SD, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 2017;26(4):611–619.e6. This study confirmed the efficacy of FMT to improve insulin sensitivity in a larger group of patients and demonstrated the major variability of response. The authors identified that low MGR before FMT was predictive of a good response to FMT.PubMedCrossRefGoogle Scholar
- 56.Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2015.Google Scholar
- 60.Aron-Wisnewsky J, Clément K. The gut microbiome, diet, and links to cardiometabolic and chronic disorders. Nat Rev Nephrol. 2015.Google Scholar
- 64.Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intesti... - PubMed - NCBI [Internet]. [cited 2019 Jun 3]. Available from: https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/31147381
- 73.Lee H, Lee Y, Kim J, An J, Lee S, Kong H, et al. Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. Gut Microbes. 2017:1–11.Google Scholar
- 81.SL et.al Effect of vegan fecal microbiota transplantation on carnitine- and choline-derived trimethylamine-N-oxide production and vascular inflammation in P... - PubMed - NCBI [internet] [cited 2019 Apr 25]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29581220