Oral FMT plus fibre supplements can improve insulin sensitivity in severely obese
Metabolic syndrome is the medical term for a combination of diabetes, high blood pressure (hypertension) and obesity. It puts you at greater risk of getting coronary heart disease, stroke and other conditions that affect the blood vessels.
Continued lack of progress in curbing this epidemic has diverted growing interest into new approaches such as fecal microbial
To establish FMT as a pragmatic therapy for obesity and metabolic syndrome, strategies that enhance efficacy using non-invasive delivery methods are needed. The concept of using dietary fiber supplementation to maintain healthy microbial
communities introduced by FMT is one strategy that has been proposed, but no human trials have examined this concept to date.
The aim of the current study therefore was to evaluate oral encapsulated FMT with adjunctive fiber supplementation in a representative North American population with severe obesity and metabolic syndrome.
The primary outcome was the evaluation of changes in insulin sensitivity between baseline and after 6 weeks of treatment using the homeostatic model assessment (HOMA2-IR/IS).
Secondary outcomes included evaluation of the safety and tolerability in addition to changes in anthropometrics, glycemic markers, lipid profile, quality of life measures, dietary intake, serum inflammatory markers, fecal SCFAs and fecal microbiota composition.
Sixty-one patients with a body mass index of 40 or higher completed the double-blind, randomized trial. Recruited from the bariatric surgery waitlist in Edmonton, US, all had metabolic syndrome.
Participants were block randomized and stratified by sex into one of four groups: FMT and high-fermentable fiber (FMT-HF (found in beans)), FMT and low-fermentable fiber (FMT-LF (found in whole grains)), placebo FMT and high-fermentable fiber (HF), and placebo FMT and low-fermentable fiber (LF).
All patients underwent concurrent medical therapy but were asked to discontinue alternative prebiotic or probiotic therapies. High-fermentable fiber supplementation consisted of an equal mixture of soluble corn fiber, resistant wheat starch type 4 and acacia gum, while low-fermentable fiber supplementation consisted of microcrystalline cellulose. The supplements were provided in foil pac kets at doses of 33g for male participants and 27g for female participants.
The fecal microbial transplants were taken by mouth in a single dose of about 20 capsules (50 g in total, with no taste or colour).
Resulting data suggests patients given a single-dose oral fecal microbial transplant followed by a daily low fermentable fibre supplement were had better insulin sensitivity and higher levels of beneficial microbes in their gut at the end of the six-week trial compared to the other patients. Improved insulin sensitivity allows the body to use glucose more effectively, reducing blood sugar.
"They were much more metabolically healthy," said principal investigator Karen Madsen, professor of medicine in the Faculty of Medicine & Dentistry and director of the Centre of Excellence for Gastrointestinal Inflammation and Immunity Research.
"These patients were on the best known medications (for metabolic syndrome) and we could improve them further, which shows us there is an avenue for improvement by targeting these different pathways in the microbiome."
Fecal transplants, which contain microbes from healthy stool donors, are currently used extensively for treating Clostridium difficile, or C. difficile, bacterial infections, and research is underway to test their usefulness in treating other illnesses such as inflammatory bowel disease, mental health and metabolic disorders.
This is the first study to show that oral delivery of fecal transplantation is effective in patients with obesity-related metabolic syndrome.
"We know that the gut microbiome affects all of these processes - inflammation, metabolism, immune function," said Madsen, who is a member of the Women and Children's Health Research Institute and is one of the University of Alberta leads for the national Microbiome Research Core (IMPACTT).
"The potential for improving human health through the microbiome is immense... We are only scratching the surface at the moment."
Our bodies do not naturally produce the enzymes needed to break down fibre, but that's what healthy bacteria in the microbiome need to live, thus the fibre supplements were important to the success of this study, Madsen said.
"When you transplant beneficial microbes, you need to feed them to keep them around. If you give a new microbe and you don't feed it, if you continue to eat a diet of processed foods and no fibre, then that microbe will likely die.
"Non-fermentable fibre can change gut motility - how fast things move through - as well as acting as a bulking and binding agent that can change levels of bile acids, which could help explain our results," Madsen explained.
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.
Madsen said the next step will be to do a longer study with more participants in multiple centres to learn how the transplant/fibre combination works and to monitor for changes in medication requirements, weight loss and other indicators. If results continue to show benefit, she said the pills could be available as a potential therapy within five years.
Source: Nature Medicine
Mocanu, V., Zhang, Z., Deehan, E.C. 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"