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: FMT; Low-abundance taxa; aFMT; core microbiome; lifestyle intervention; weight regain.

Figure 1.

Trial flow chart. ‘Microbiome analysis’ refers to Figure 2. ‘Weight maintenance analysis’ refers to Figure 3.

Figure 2.

Bacterial species, stratified by phyla, are presented as a singular bar along the X-axis, as the same vertical bar along the entire figure represents the same species. (a). presence/absence matrix at baseline, red indicates presence. Each row represents a participant. classification to the core and non-core taxa based on the presence/absence matrix, green represents core. (b). species prevalence across all participants. (c). species mean relative abundance across all participants. (d). median log₂ species 6m change across all participants. (e). T-test comparison of core and non-core 6m absolute median log₂ change.

Figure 3.

(a). subject-specific Jaccard index for the core and non-core microbiome fractions, their correlation, and division to four “high/low core/non-core change” groups based on linear regression. (b). 8-14m weight regain comparison between aFMT and placebo within each “core/non-core” sub-group. T-tests were used to compare weight maintenance between treatment and placebo within each group.