Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain

Ehud Rinott, Ilan Youngster, Anat Yaskolka Meir, Gal Tsaban, Hila Zelicha, Alon Kaplan, Dan Knights, Kieran Tuohy, Francesca Fava, Matthias Uwe Scholz, Oren Ziv, Elad Reuven, Amir Tirosh, Assaf Rudich, Matthias Blüher, Michael Stumvoll, Uta Ceglarek, Karine Clement, Omry Koren, Dong D. WangFrank B. Hu, Meir J. Stampfer, Iris Shai

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71 Scopus citations


Background & Aims: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase. Methods: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3–4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6–14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet. Results: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6–14 (aFMT, 30.4% vs placebo, 40.6%; P = .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02), but not in the dietary guidelines (P = .57) or Mediterranean diet (P = .64) groups (P for the interaction = .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P = .01) and insulin rebound (aFMT, –1.46 ± 3.6 μIU/mL vs placebo, 1.64 ± 4.7 μIU/mL; P = .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction = .04 and. 03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss–associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet–induced regain phase (all, P < .05). Conclusions: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.

Original languageEnglish
Pages (from-to)158-173.e10
Issue number1
StatePublished - Jan 2021

Bibliographical note

Funding Information:
Funding This work was supported by the Israeli Science Foundation (grant 1733/18 ), Israel Ministry of Health (grant no. 87472511 ), Israel Ministry of Science and Technology (grant 3-13604 ); Deutsche Forschungsgemeinschaft (German Research Foundation), Projektnummer 209933838–SFB 1052; the Deutsche Forschungsgemeinschaft, Obesity Mechanisms ; the Rosetrees trust (grant A2623 ); the Project Cabala_diet&health ( http://www.cabalaproject.eu/ ; ERA-Net Cofund ERA-HDHL N696295), and the California Walnuts Commission. Dong D. Wang’s research was supported by research grants from the National Institutes of Health ( K99 DK119412 ) and the Boston Nutrition Obesity Research Center. None of the funders were involved in any stage of the design, conduct, or analysis of the study, and had no access to the study results before publication.

Publisher Copyright:
© 2021 The Authors


  • Autologous FMT
  • Diabetes
  • Obesity
  • Weight Regain After Diet


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