A double-blind, placebo-controlled, phase 2 trial found that a single-dose oral fecal microbial transplantation (FMT) and daily low-fermentable fiber supplement improved insulin resistance and sensitivity among patients with severe obesity and metabolic syndrome. These findings were published in Nature Medicine.

Patients (N=70) with severe obesity (body mass index [BMI] >30) and metabolic syndrome were recruited at the Weight Wise Bariatric Clinic in Canada between 2018 and 2019 for this proof-of-concept trial. The participants were randomly assigned to receive FMT with high-fermentable fiber (FMT-HF; n=17), FMT with low-fermentable fiber (FMT-LF; n=17), placebo with high-fermentable fiber (HF; n=17), or placebo with low-fermentable fiber (LF; n=19).

The FMT or placebo was administered as a single dose, and the fiber supplement was given daily for 6 weeks. Changes in insulin sensitivity, insulin resistance, and microbiota diversity were assessed through 12 weeks.


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The participants had a mean age of 47.8±10.0 years, 83.6% were women, their BMI was 45.3±7.0. Of the participants, 63.9% were taking glucagon-like peptide-1, and 24.6% were using conventional metformin.

At 6 weeks, the homeostatic model assessment of insulin resistance was significantly improved compared with baseline among the FMT-LF group (mean, 3.16±3.01 vs 3.77±3.57; P =.02) but not among the FMT-HF (mean, 3.25±1.70 vs 3.17±1.72; P =.8), LF (mean, 3.76±2.01 vs 3.56±1.81; P =.8), or HF (mean, 3.49±1.43 vs 3.26±1.33; P =.8) cohorts.

The FMT-LF recipients had significant improvements in serum insulin levels (mean difference, -25.4%±12.3%; P =.02) at 6 weeks.

A homeostatic model assessment of insulin resistance improvement was associated with FMT-LF vs LF assignment (odds ratio [OR], 23.4; 95% CI, 2.8-193.3; P =.003) and increased baseline serum insulin (OR, 2.01; 95% CI, 1.19-3.41; P =.009). An improved homeostatic model assessment of insulin sensitivity was associated with FMT-LF vs LF assignment (OR, 16.6; 95% CI, 2.19-125.8; P =.007) and increased baseline serum insulin (OR, 1.87; 95% CI, 1.13-3.11; P =.015).

The FMT-LF treatment was associated with increased bacterial richness as compared with baseline (q <.01). The beta diversity was significantly increased among both FMT cohorts (q <.02). Specifically, the FMT-LF group had increases to the taxa Phascolarcobacterium, Christensenellaceae, Bacteroides, and Akkermansia muciniphila and decreases to Dialister and Ruminococcus torques. These perturbations were maintained through the 12-week follow-up.

This study was limited by its small sample size and did not have sufficient power to detect significant differences for the full spectrum of metabolic outcomes.

These data indicated that a single-dose FMT with daily low-fermentable fiber supplementation significantly improved insulin resistance and sensitivity among individuals who were severely obese with metabolic syndrome.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of authors’ disclosures.

Reference

Mocanu V, Zhang Z, Deehan EC, et al. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial. Nat Med. 2021;27(7):1272-1279. doi:10.1038/s41591-021-01399-2