The potential benefits of fecal microbiota transplantation in obesity could rely on supplementation of low-fermentable fiber

Image source: Cell Rep Med.

Although current research supports the role of fecal microbiota transplantation (FMT) mainly in recurrent Clostridioides difficile infection, emerging evidence suggests it could also work for other conditions such as inflammatory bowel disease and non-infectious diseases, including metabolic syndrome and obesity.

A new proof-of-principle randomized double-blind, placebo-controlled trial has found that supplementing low fermentable fiber after FMT may improve insulin sensitivity in individuals with severe obesity.

The authors compared the efficacy on insulin sensitivity, assessed by the homeostatic model assessment (HOMA2-IR/IS), of high and low fermentable fiber supplementation in patients with severe obesity and metabolic syndrome receiving and not receiving FMT (in form of encapsulated donor feces) from a lean donor.

Low-fermentable fiber supplementation (consisting of cellulose at doses of 27 g/day to 33 g/day) following oral FMT significantly improved insulin-resistance marker HOMA2-IR/IS and decreased serum insulin at 6 weeks, with participants with baseline poor insulin regulation having the better response. However, no differences in insulin sensitivity were found for participants receiving high-fermentable fiber supplementation and oral FMT, high-fermentable fiber alone or low-fermentable fiber alone. None of the interventions were related to serious adverse events.

Beyond improving insulin sensitivity, low-fermentable fiber supplementation and oral FMT also improved engraftment of the donor microbiota at 6 weeks and restored the responses of serum GLP-1—an incretin hormone involved in the augmentation of glucose-stimulated insulin secretion—to an oral glucose tolerance test.

Although FMT and low-fermentable fiber led to an increase in fecal microbiota richness both at 6 and 12 weeks from baseline, the authors reported that improvements in insulin sensitivity were not maintained after a follow-up at 12 weeks in the absence of fiber intake. Interestingly, specific bacterial taxa at baseline (Phascolarctobacterium, Bacteroides stercoris and B. caccae) acted as predictors of insulin sensitivity.

The study’s major caveats include its methodology (i.e., within-group comparisons), the small sample studied and the lack of homogeneity of the four donor samples under study, which is a known bias in the field.

The findings suggest that the potential application of FMT in obesity is driven in part by the living microbial fraction and its engraftment in recipient individuals, as Nordin M. J. Hanssen and Max Nieuwdorp acknowledge in a spotlight article in Cell Reports Medicine summarizing research from Mocanu et al.

Although the preliminary nature of the study needs to be replicated, the results highlight the role of fiber in increasing the potency of FMT, supporting the potential role of gut microbiome modulation as a novel treatment for improving metabolic health. The study also highlights the importance of standardizing FMT preparation and delivery and studying in great detail the diet of donors, which can contain other nutrients beyond fiber that can affect FMT’s efficacy.

References:

de Groot PF, Frissen MN, de Clercq NC, et al. Fecal microbiota transplantation in metabolic syndrome: History, present and future. Gut Microbes. 2017; 8(3):253-267. doi: 10.1080/19490976.2017.1293224.

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.

Hanssen NMJ, Nieuwdorp M. Fecal microbiota transplantation and fiber supplementation, better together? Cell Rep Med. 2021; 2(9):100403. doi: 10.1016/j.xcrm.2021.100403.