Fiber medicine

Fecal transplantation and fiber improve insulin in obesity

As the use of fecal microbial transplantation evolves, new research shows that a non-invasive approach – with an oral capsule formulation – combined with fiber supplementation significantly improves insulin sensitivity in people suffering from severe obesity and metabolic syndrome.

“We believe this noninvasive approach will replace invasive fecal microbial transplantation,” said lead author Karen L. Madsen, PhD. Medscape Medical News.

The findings of Madsen, Center of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta School of Medicine and Dentistry, Edmonton, Alberta, Canada, and his colleagues were published this week in natural medicine.

“The potential for improving human health through the microbiome is immense,” Madsen said in a press release from his institution. “We’re only scratching the surface at the moment.”

The study builds significantly on previous findings, says Amir Zarrinpar, MD, PhD, of the Division of Gastroenterology at the University of California, San Diego, who was not involved in this work.

“I think it’s exciting that the study replicates previous findings. [from a smaller study] showing that modulating the microbiome with a fecal microbial graft resulted in a 6-week change in insulin sensitivity…and that these results can be replicated with oral fecal microbial graft tablets with fiber supplements, when a previous to study daily administration of oral capsules did not find a significant difference” in metabolic outcomes in obese patients, he said.

Capsules, fiber supplementation, effects beyond C diff

Fecal transplants, which contain microbes from healthy stool donors, have been shown to provide substantial benefits in the treatment of Clostridium difficile infection using a colonoscopy or, less commonly, a nasoduodenal tube for transplantation.

Interest has grown in the potential use of the approach for a wide range of other conditions thought to be influenced by the gut microbiome, and researchers are investigating non-invasive alternatives for administering the fecal microbial material.

To examine this approach in patients with obesity/metabolic syndrome―and to test the theory that fiber supplementation might further improve treatment response―Madsen and his team recruited 61 patients with metabolic syndrome (mass index body ≥ 40).

Patients were randomly assigned in a double-blind fashion to two groups. One group received a daily powder supplement containing a highly fermentable fiber, such as that found in beans. The other group received a similar supplement of low-fermentation fiber — essentially cellulose — found in whole grains. The goal was to see if different fibers would have different effects.

Within each of the fiber supplementation groups, the patients were then divided into two subgroups. A subgroup received either a single-dose regimen of 20 oral capsules of fecal transplant material from healthy donors; the other received the same quantity of capsules containing a placebo. The capsules had no taste or smell.

All groups had 17 patients, except the non-fermentable fiber/oral faecal transplant group which had 19.

For the primary endpoint of change in insulin sensitivity from baseline to week 6, determined using the homeostatic model assessment (HOMA2-IR/IS), significant improvements were observed only in patients in the fecal microbial transplant and low-fermentation fiber supplement group, with a mean improvement in HOMA2-IR score from 3.77 at baseline to 3.16 at 6 weeks (P = .02).

Importantly, the improvements were seen after adjusting for a host of factors, including diet and medication.

There were no differences between groups in secondary outcomes of fasting blood glucose or A1c at 6 weeks. A 12-week follow-up showed that improvements in insulin sensitivity were not maintained if daily fiber intake was not continued.

It should be noted that for all patients there were significant reductions in blood pressure except those in the highly fermentable fiber supplement group. Additionally, those in the low-fermentation fiber supplement group lost weight at week 12.

The interventions were safe and well tolerated, with no serious treatment-related adverse events.

Can low fermentation fiber amplify the effects of fetal microbial transplantation?

Because patients were selected from a bariatric surgery waiting list, all were already receiving medical treatment and dietary advice from a bariatric team.

“The exciting findings were that we were able to improve the subject’s metabolic health even when they were on the gold standard of available therapy,” Madsen said.

She hypothesized that fiber supplementation could be the key to the benefits by acting to counter the otherwise gradual loss of fecal microbial matter from the donor.

“If you give a new microbe and you don’t feed it, [and] if you continue to eat a diet of processed, fiber-free foods, this microbe will likely die,” she explained.

“Although this study did not compare fecal microbial grafting plus low-fermentation fiber with fecal grafting alone, it is provocative that low-fermenting fiber may amplify the effects of fecal microbial grafting,” Zarrinpar said.

Ultimately, “we need larger studies with more participants and more analyzes of what’s going on in the gut microbiome to better understand how fecal microbial grafting can affect host physiology,” he concluded.

The authors and Zarrinpar have disclosed no relevant financial relationship.

NatMed. Published online July 5, 2021. Summary

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