A single fecal microbiota transplant in obese teens was linked to long-lasting metabolic improvements, including smaller waistlines, reduced body fat, lower inflammation, and better cholesterol levels, with some benefits still evident four years later.
We’ve covered fecal transplantation studies before. While it might not be an appropriate topic for dinner table conversation, the rise in research acknowledging the importance of the gut microbiome on pretty much the entire body has shone a spotlight back on the treatment.
Eight years ago, 87 adolescents participated in a groundbreaking study led by the University of Auckland, New Zealand, in which they received a single fecal microbiota transplant (FMT) to treat their obesity. The researchers have now published the results of their follow-up study, conducted more than four years later.
“What is impressive is that just a single FMT treatment produced a dramatic reduction in metabolic syndrome that lasted at least four years,” said Wayne Cutfield, MD, a Professor of Pediatric Endocrinology at the Liggins Institute at the University of Auckland and the study’s co-corresponding author. “This means participants are at much lower risk of developing diabetes and heart disease over the long term.”
The eighty-seven obese adolescents recruited into the trial were aged between 14 and 18. Half received FMT capsules – yes, taken via the mouth – made from healthy, lean donors. The others received placebo capsules. Participants in the treatment group swallowed 28 capsules over two days, each containing gut bacteria from four donors. For the first six months, the trial was a double-blind, randomized, placebo-controlled trial. And, no effect on body mass index (BMI) or total body fat, the primary outcomes, was seen. After that, participants were unblinded (that is, they knew whether they’d received treatment or a placebo) but followed up four years later.
After around four-and-a-half years, 55 participants (63% of the original group) came back for checks that included DEXA body scans, blood tests, blood pressure measurements, diet and activity questionnaires, and stool samples for gut microbiome analysis. A DEXA (dual-energy X-ray absorptiometry) scan is a non-invasive medical imaging test that uses low-dose X-rays to accurately measure a person’s bone density, total body fat, and lean muscle mass.
The researchers found that while there were no significant differences in weight and BMI between the FMT and placebo groups, those who’d had FMT had smaller waistlines (10 cm/3.9 in on average) and around 5% less total body fat on follow-up. They had lower severity scores for metabolic syndrome, much lower inflammation, and higher levels of “good” HDL cholesterol. No major difference was seen in blood sugar control or most other cholesterol and lipid markers.
“More than one in three of the original teenage participants in our study had metabolic syndrome,” Cutfield said. “Metabolic syndrome has severe consequences, including a doubling in risk of death from heart disease or stroke and a five-fold increased risk of type 2 diabetes.”
Astonishingly, FMT led to long-lasting changes in gut bacteria and viruses. The donor-derived bacterial and viral strains that participants in the treatment group had taken were still present after four years. On average, 23% of gut strains in the FMT group were donor-derived, even after this time. Some participants retained many donor strains, others very few.
These results don't prove that FMT prevents diabetes or heart disease; rather, they suggest a possible effect that needs confirmation in larger, blinded trials.
“It really makes us think about the timeframes over which we look for the impacts of microbiome-based treatments,” said the study’s other corresponding author, Professor Justin O’Sullivan, PhD, Director of the Liggins Institute. “Imagine being able to program your microbiome to reduce the risk of conditions before they occur. This work is paving the way for next-generation probiotics that target specific conditions through sustained changes to the microbiome.”
Commercialization of a microbiome-based treatment for metabolic syndrome is the researchers’ end goal.
“Our holy grail is to develop a super mix of bacteria that can be taken to prevent or moderate metabolic syndrome,” said Cutfield. “The first step is to prove our bespoke combination of bacteria actually works.”
The study was published in the journal Nature Communications.
Source: University of Auckland
