Fecal Microbiome Transplant Not Much Help in Pediatric Obesity

A mixed bag of outcomes was seen after fecal microbiome transplantation (FMT) using oral capsules in adolescents with obesity, according to a randomized trial.

Looking at 87 kids from New Zealand, those who underwent a single course of an oral encapsulated FMT didn’t see a significant benefit in regard to body mass index (BMI) standard deviation score after 6 weeks (adjusted mean difference [aMD] -0.026, 95% CI -0.074 to 0.022), reported Justin O’Sullivan, PhD, of the University of Auckland in New Zealand, and colleagues in JAMA Network Open.

However, the fecal transfer did yield some other benefits, including a significant reduction in android-to-gynoid-fat ratio at several time points compared with placebo:

• After 6 weeks: aMD -0.021 (95% CI -0.041 to -0.001)
• After 12 weeks: aMD -0.023 (95% CI -0.043 to -0.003)
• After 26 weeks: aMD -0.029 (95% CI -0.049 to -0.008)

A post-hoc exploratory analysis also found that kids with obesity who fit the criteria for metabolic syndrome at baseline were more likely to have their metabolic syndrome resolved 26 weeks later with FMT compared to the placebo group (adjusted odds ratio 0.06, 95% CI 0.01-0.45, P=0.007). In total, only four of the 18 participants with metabolic syndrome at baseline still had the condition after their fecal transfer. In contrast, 10 of 13 cases of metabolic syndrome remained in the placebo group.

Those who received the FMT also saw a bit of a shift in community composition as seen via gut microbiome profiling, with this shift maintained for up to 12 weeks after the transfer.

This was largely where the advantages ended, though, as there weren’t any significant benefits in insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, nor health-related quality of life after the fecal transfer.

The transfer was safe, with no participants experiencing any serious adverse events. The most common minor adverse events reported were loose stools, changes in frequency of bowel movements, and abdominal pain.

“We believe that FMT can be a feasible future treatment for obesity and/or metabolic diseases, but it is likely targeted microbial therapy with a defined, cultured microbial mixture would be more socially acceptable and safe,” the researchers pointed out.

They suggested that future trials in this area “therefore focus on identifying the organisms and mechanisms that were responsible for mediating the observed benefits in the presence of dietary restriction.”

The double-blind trial included 42 post-pubertal adolescents who underwent the FMT compared with 45 who received placebo. Participants were ages 14 to 18 and had a BMI of 30 or greater at baseline.

The fecal microbiome came from eight healthy, lean donors — four men and four women — with the microbiome double encapsulated with delayed-release hydroxypropyl methylcellulose capsules (Capsugel).

Prior to the transfer, the participants did a bowel cleanse using an oral 70-g bowel lavage solution the day prior, followed by an overnight fast. Each participant received seven capsules from each of the same-sex donors for a total of 28 capsules over 2 days (total of about 22 grams of wet weight of fecal material).

Within the initial 6 weeks after the transfer, adolescents who received the intervention did see a significant decline in BMI, but this improvement compared with placebo disappeared after 6 weeks (BMI standard deviation score aMD 0.91, 95% CI 0.34-1.49, P<0.001). Similarly, those who received the intervention also saw a significant 34% improvement in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), a 29% reduction in fasting insulin, and a 7% reduction in fasting glucose within the first 6 weeks after the transfer, but these were likewise not maintained.