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Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain
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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.
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“Fasting may affect weight control by altering the composition of the gut microbiota [76, 96]”
From Comparing caloric restriction regimens for effective weight management in adults: a systematic review and network meta-analysis (2024) · cites this paper as [96]
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“These findings have been confirmed in humans, as autologous FMT, collected during a lean phase and re-infused during a regain phase in obese or dyslipidemic patients, was able to attenuate weight gain and insulin rebound. 112”
From Key determinants of success in fecal microbiota transplantation: From microbiome to clinic (2023) · cites this paper as [112]
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Self-citationAll Diets Work the Same—But Some Work More Equally
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Metadata
- Authors
- Rinott, E., Youngster, I., Yaskolka Meir, A., Tsaban, G., Zelicha, H., Kaplan, A., Knights, D., Tuohy, K., Fava, F., Scholz, M. U., Ziv, O., Rubin, E., Tirosh, A., Rudich, A., Blüher, M., Stumvoll, M., Ceglarek, U., Clement, K., Koren, O., Wang, D. D., Hu, F. B., Stampfer, M. J., & Shai, I.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Tel Aviv University (IL)
- University of Minnesota (US)
- Fondazione Edmund Mach (IT)
- Bar-Ilan University (IL)
- Brigham and Women's Hospital (US)
- Leipzig University (DE)
- Harvard University (US)
- Corresponding author
- Youngster, Ilan
- Shai, Iris
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 160
- Issue
- 1
- Pages
- 158-173.e10
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC7755729
- OpenAlex
- W3081134517
- Cited by
- 192
- References
- 38
- Citations by year
- 2026: 26 · 2025: 30 · 2024: 41 · 2023: 30 · 2022: 40 · 2021: 22
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Gastroenterology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutional Research Information System (Fondazione Edmund Mach) (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (209933838–SFB 1052)
- Israel Science Foundation
- National Institutes of Health (K99 DK119412)
- Ministry of Science and Technology, Israel
- California Walnut Commission
- Ministry of Health, State of Israel
- Nutrition Obesity Research Center at Harvard
- Rosetrees Trust (A2623, ERA-HDHL N696295)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- weight regain, weight loss maintenance, Mediterranean diet, polyphenols, green tea, Juglans regia, Wolffia globosa, gut microbiota, obesity, dyslipidemia, dietary intervention, 16S rRNA gene sequencing, metagenomics, physical activity
- MeSH terms
- Fecal Microbiota Transplantation, Adult, Animals, Disease Models, Animal, Female, Humans, Israel, Life Style, Male, Middle Aged, Obesity, Weight Gain, Weight Loss, Exercise, Diet, Mediterranean, Mice, Waist Circumference
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