Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial

ABSTRACT

We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0–6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = −8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m’s fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P < .0001). Subject-specific changes in core and non-core taxa fractions were strongly correlated (Jaccard Index; r = 0.54; P < .001). Following aFMT treatment, only participants with a low 6 m change in core taxa, and a high change in non-core taxa, avoided 8–14 m weight regain (aFMT = −0.58 ± 2.4 kg, corresponding placebo group = 3.18 ± 3.5 kg; P = .02). In a linear regression model, low core/high non-core 6 m change was the only combination that was significantly associated with attenuated 8–14 m weight regain (P = .038; P = .002 for taxa patterns/treatment intervention interaction). High change in non-core, low-abundance taxa during weight-loss might mediate aFMT treatment success for weight loss maintenance.

ClinicalTrials.gov: NCT03020186

KEYWORDS:

• core microbiome
• Low-abundance taxa
• aFMT
• weight regain
• FMT
• lifestyle intervention

Acknowledgments

We thank Prof. Assaf Rudich for his review of the manuscript of this work.

Disclosure statement

Iris Shai advises the nutritional committee of Hinoman, Ltd. Ilan Youngster is an advisor for Mybiotics Ltd. Dan Knights is CEO of, and holds equity in, CoreBiome, Inc.

Data availability statement

As previously reported⁷, shotgun metagenomic sequencing data have been deposited in the European Nucleotide Archive with accession number PRJEB49147 (https://www.ebi.ac.uk/ena/browser/view/PRJEB49147)

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2264457

Additional 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 (DFG, German Research Foundation), Projektnummer 209933838–SFB 1052: “Obesity Mechanisms”; the Rosetrees trust (grant A2623); the Project Cabala_diet&health (http://www.cabalaproject.eu/; ERA-Net Cofund ERA-HDHL N696295), the California Walnuts Commission, and National Institutes of Health ((R01NR019992 and R00DK119412). 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