Metabolic improvements seen 26 weeks after fecal microbiome transfer for teens
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Fecal microbiome transfer led to a mean reduction in android-to-gynoid fat ratio and a resolution of metabolic syndrome in a cohort of adolescents with obesity, according to randomized controlled trial data published in JAMA Network Open.
“Single treatment microbiome transfers can impact the composition of low-complexity gut microbiomes within recipients,” Justin M. O’Sullivan, PhD, and Wayne Cutfield, MD, professors in the Liggins Institute at the University of Auckland, told Healio. “The effects that are associated with this transfer are linked to metabolic syndrome and also sex-specific changes.”
O’Sullivan, Cutfield and colleagues conducted a two-armed randomized controlled trial in which participants received an encapsulated fecal microbiome or placebo. All participants were aged 14 to 18 years with obesity and without prediagnosed chronic disease that could affect weight or metabolism. Before intervention, all participants had a bowel cleanse and fasted overnight for at least 8 hours. Fecal microbiome was extracted from four healthy men and four healthy women after a screening process. Each participant received seven capsules from each of the four same-sex donors for a total of 28 capsules over 2 consecutive days. A clinical assessment was conducted at intervention as well as at 6-, 12- and 26-weeks of follow-up.
There were 87 participants in the trial (58.6% female; mean age, 17.2 years) with 42 receiving fecal microbiome transfer and 45 receiving placebo. The fecal microbiome cohort had a lower android-to-gynoid fat ratio at 6 weeks (adjusted mean difference [AMD], –0.021; 95% CI, –0.041 to –0.001; P = .042), 12 weeks (AMD, –0.023; 95% CI, –0.043 to –0.003; P = .028) and 26 weeks (AMD, –0.029; 95% CI, –0.049 to –0.008; P = .0069) compared with placebo. The android-to-gynoid fat ratio decrease was more prominent among female participants. No effect was observed on BMI in the fecal microbiome transfer group at any of the follow-up visits. Insulin sensitivity, liver function, lipid profile, inflammatory markers, total body fat percentage and clinic blood pressure were not affected by fecal microbiome transfer. The treatment group had a lower systolic BP at 6 weeks compared with placebo (AMD, 2.5 mm Hg; 95% CI, 0.3-4.7; P = .024).
In post hoc analysis of participants with undiagnosed metabolic syndrome at baseline, 18 of 22 in the fecal microbiome transfer group had metabolic syndrome resolution at 26 weeks. After 6 weeks, fecal microbiome transfer was associated with a 34% improvement in insulin resistance, a 29% reduction in fasting insulin and a 7% reduction in fasting glucose. These changes did not persist at later follow-up.
There were no serious adverse events reported during the trial. Minor adverse events were rare and unrelated to treatment, and no participant reported discomfort or difficulty ingesting the treatment capsules.
While there was no mean weight loss in the fecal microbiome treatment cohort, O’Sullivan and Cutfield said the improvements in android-to-gynoid fat ratio and metabolic syndrome were achieved without control the diet. The next steps are to evaluate the fecal microbiome transfer alongside dietary changes.
“We know we changed the microbiome out to 26 weeks in recipients,” O’Sullivan and Cutfield said. “Anecdotally it seems that several individuals underwent calorie restriction diets with their new gut microbiomes and lost large amounts of weight (> 10 kg) in a short time. This is consistent with mouse data in which the combination of regulated food intake and the gut microbiome from lean mice led to weight reduction in obese mice.”
For more information:
Justin M. O’Sullivan, PhD, can be reached at justin.osullivan@auckland.ac.nz.
Wayne Cutfield, MD, can be reached at w.cutfield@auckland.ac.nz.
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