Oral Fecal Microbial Transplant Plus Fiber Improves Insulin Metrics of Patients With Severe Obesity

Insulin pen.
The researchers tested whether daily fiber supplementation in addition to fecal microbial transplantation would improve cardiometabolic outcomes among severely obese patients.

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.

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.


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