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Fecal Transplants Need The Right Support



The fact that the gut microbiota plays an important role in digestion and metabolism should by now be common knowledge. There is now also abundant evidence that obesity is associated with a rarefied microbiome, the causes for which are not entirely clear. 

One of the more adventurous approaches to rectifying this issue has been the idea of using fecal transplants from lean people in an attempt to ‘repoopulate’ (pardon the pun) the gut of people living with obesity.

In one such study by Valentin Mocanu and colleagues from the University of Alberta, in which I happened to be peripherally involved, now published in Nature Medicine, suggests that it may not be enough to just transplant the bugs, but that you also need to support them.

The double-blind study involved 70 volunteers with severe obesity and metabolic syndrome, who were randomised into two groups, one receiving fecal transplants from lean donors (in the form of capsules) vs. placebo capsules. Each of these groups were then further randomised to receive daily supplements of either high-fermentable (HF) or low-fermentable (LF) fiber over 6 weeks. 

This treatment resulted in a significant improvement in HOMA as a measure of insulin resistance in the Fecal-Microbial-Transplant-Low-Fermentable fibre group (FMT-LF), with no changes in any of the other groups. In addition, there was also restoration of the physiologic patterns of GLP-1 secretion in the FMT-LF group. 

As for the microbiome itself, the FMT-LF intervention was associated with increases in bacterial richness (Chao1 index) from baseline to week 6 with the FMT-LF intervention resulting in changes in seven genera and 12 amplicon sequence variants (ASVs), several of which were detectable at week 6, including increases in the relative amounts of Phascolarcobacterium, Christensenellaceae, Bacteroides and Akkermansia muciniphila and decreases in Dialister and Ruminococcus torques.

Most of these changes were no longer apparent after 12 weeks. 

As for why these changes were only seen in the FMT-LF group, the authors have the following speculation to offer,

Possible explanations include the ability of cellulose to act as a bulking and binding agent, which could alter metabolite luminal concentrations, influence gastrointestinal transit and modulate the donor microbe–host mucus layer interface. Cellulose supplementation may also directly alter the function of specific taxa, including cellulose-degrading H2-producing methanogens, leading to changes in gut microbial fermentation efficiency and by-products. Together these factors might constitute mechanisms through which the FMT-LF intervention increases microbial diversity and richness while also potentially inducing functional changes in taxa associated with host HOMA2-IR/IS improvements.

Irrespective of the actual mechanisms, the study does suggest that daily low-fermentable fiber supplementation may be needed to support an FMT intervention to  improve insulin sensitivity, and may perhaps act by differentially modulating engraftment of select bacterial taxa and the enteroendocrine axis. 

Whether or not this approach will ever translate into a viable treatment for patients with metabolic syndrome remains to be seen. 

@DrSharma
Berlin, D

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