Journal Article

Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial

Zhang, Zhengxiao, Hotte, Naomi, Kao, Dina H., Karmali, Shahzeer, Madsen, Karen L., Samarasinghe, Kalutota K., Deehan, Edward C., Walter, Jens, Mocanu, Valentin, Birch, Daniel W.

2021

Overview

Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF ( n  = 17), FMT-LF ( n  = 17), HF ( n  = 17) and LF ( n  = 19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6 weeks using the homeostatic model assessment (HOMA2-IR/IS). After 6 weeks, only patients in the FMT-LF group had significant improvements in HOMA2-IR (3.16 ± 3.01 at 6 weeks versus 3.77 ± 3.57 at baseline; P  = 0.02). No difference in HOMA2-IR was observed over this period for those in the FMT-HF group (3.25 ± 1.70 at 6 weeks versus 3.17 ± 1.72 at baseline; P  = 0.8), the HF group (3.49 ± 1.43 at 6 weeks versus 3.26 ± 1.33 at baseline; P  = 0.8) or the LF group (3.76 ± 2.01 at 6 weeks versus 3.56 ± 1.81 at baseline; P  = 0.8). Interventions were safe and well-tolerated with no treatment-attributed serious adverse events. We provide proof of concept for the use of a single-dose oral FMT combined with daily low-fermentable fiber supplementation to improve insulin sensitivity in patients with severe obesity and metabolic syndrome. Results from a phase 2 randomized controlled trial demonstrate improved insulin sensitivity in patients with severe obesity and metabolic syndrome following single-dose fecal microbial transplantation and daily supplementation with low-fermentable fiber for 6 weeks.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/326/2565/2134 / 692/699/2743/2037 / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Dietary Fiber - therapeutic use / Dietary Supplements / Dosage / Double-Blind Method / Double-blind studies / Fecal Microbiota Transplantation - methods / Feces / Female / Fermentation - physiology / Fiber in human nutrition / Gastrointestinal Microbiome - physiology / Health aspects / Humans / Infectious Diseases / Insulin / Insulin Resistance - physiology / Male / Metabolic Diseases / Metabolic disorders / Metabolic syndrome / Metabolic Syndrome - therapy / Microorganisms / Middle Aged / Molecular Medicine / Neurosciences / Obesity / Obesity, Morbid - therapy / Patients / Placebos / Proof of Concept Study / Testing / Transplantation