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

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.

Pilot study of autologous fecal microbiota transplants in nursing home residents: Feasibility and safety.

Introduction: Antibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population. Methods: Pilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE). Results: We screened 468 nursing home residents aged ≥18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2 ± 8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention. Conclusions: In this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe. Trial registration: ClinicalTrials.gov Identifier: NCT03061097.

Autologous fecal microbiota transplantation can retain the metabolic achievements of dietary interventions.

BACKGROUND: We recently reported that autologous fecal microbiota transplantation (aFMT), derived from the time of maximal weight-loss and administrated in the regain-phase, might preserve weight loss and glycemic control in moderately obese subjects, and is associated with specific microbiome signatures. Here, we sought to explore the global effect of aFMT on adipokines, inflammatory markers and blood cholesterol and on the overall gut microbiome preservation. METHODS: In the DIRECT-PLUS weight-loss trial, abdominally obese participants were randomized to three distinct weight-loss diets. Following the expected weight loss phase (0-6 m), 90 participants were randomized to receive their personal frozen fecal microbiota or placebo oral capsules (ten 1 g-capsules over ten sessions-total=100 g) during the expected weight regain phase (8-14 m). RESULTS: Of the 90 participants (age=52 yr; 0-6 m weight loss=-8.3 kg), 95.6% ingested at least 80/100 oral aFMT/placebo capsules over 6 months. Overall, the gut microbiome community structure was associated with plasma levels of leptin, cholesterol and interleukin-6 at baseline and after 6 m, whereas 6 m (weight loss phase) changes in specific microbiome species associated with the dynamic of leptin and inflammatory biomarkers. Following the 8-14 m aFMT administration phase, aFMT maintained decreased levels of leptin (ΔaFMT=-3.54 ng/mL vs. Δplacebo=-0.82 ng/mL;P = 0.04), C-reactive-protein (ΔaFMT=-1.45 mg/L vs. Δplacebo=-0.66 mg/L;P = 0.009), Interleukin-6 (ΔaFMT=-0.03pg/mL vs. Δplacebo=1.11pg/mL;P = 0.03) and total cholesterol (ΔaFMT=2.2 mg/dl vs. Δplacebo=13.1 mg/dl;P = 0.04) achieved in the weight loss phase. Overall, aFMT induced a significant preservatory effect on personal gut microbiome global composition (P = 0.03;Jensen-Shannon distance), as compared to placebo. CONCLUSIONS: aFMT treatment in the regain phase might retain weight-loss induced metabolic benefits. These findings may suggest a novel aFMT treatment approach for personal metabolic attainment preservation.