麻豆传媒

SAN DIEGO -- Can fecal microbiota transplantation (FMT) help treat obesity and diabetes?

Two studies presented this week at demonstrated that FMT can safely lead to sustained changes in recipients' microbiomes. Whether that will translate into actually helping patients lose weight or treat their diabetes, however, remains to be seen.

"There is a paucity of effective pharmacologic therapies currently [to treat obesity], and while surgery is available, it is invasive and accompanied by significant morbidity," said Director, Fecal Microbiota Transplant Program, Brigham and Women's Hospital, Boston, during one of the presentations. "We really do feel there is an urgent need for novel treatment strategies targeted at the underlying pathology."

In their pilot study, Allegretti and her colleagues evaluated 22 obese individuals (BMI ≥35), without any conditions associated with obesity, such as diabetes or metabolic syndrome. In this 12-week trial, half of the participants received an induction of 30 FMT capsules, with additional 12-capsule doses at 4 and 8 weeks, while the others received placebo. The FMT capsules came from a single female "lean" donor with a BMI of 17.

The study's primary outcomes were the procedure's safety and its effects on glucagon-like peptide-1 (GLP-1), which is associated with the satiety reflex and associated with weight gain and loss.

While the procedure appeared relatively safe (no adverse events worse than grade 1), no increase in the area under the curve for GLP-1 in either group at 12 weeks compared to baseline. And no change in mean body weight was seen.

But participants' microbiota did change with FMT, with the microbial makeup of their stools becoming more similar to that of the donor. Allegretti and colleagues also noticed alterations in patients' bile acid profiles.

Allegretti said her group believed 12 weeks was not enough to see changes in body weight, and therefore it wasn't a primary outcome in the trial.

"I think this is really a hypothesis-generating study," said Allegretti. "There's a lot we don't know. Who are the patients that will benefit from this? Is this the right cohort of obese patients that will benefit from this therapy? I think it's unclear."

"We also went with the lean donor hypothesis," she noted. " Is that the right donor and is that the right dose? The next obvious step for us is to do more dose-finding work."

Findings were similar in the second study, led by , of Massachusetts General Hospital and Harvard Medical School in Boston. Conducted over 12 weeks, its goal also was to evaluate whether FMT capsules would alter the recipient's intestinal microbiome and affect certain metabolic biomarkers -- particularly insulin sensitivity -- in obese persons.

As in Allegretti's study, FMT engraftment was successful, but metabolic outcomes were unchanged, leading Yu to conclude that "microbial manipulation by FMT capsules alone may not meaningfully alter metabolic outcomes in unselected obese recipients."

"These two findings are actually fairly consistent with previous ones that were published, which is that fecal transplant is not going to be a silver bullet for obesity," said , of the University of California San Diego, who moderated the session at DDW.

Zarrinpar told 麻豆传媒 that these two studies, as well as , "have been investigational in the sense they've given fecal transplants without doing what we would normally do to treat obesity, which is have patients see a nutritionist, and have them go through behavioral therapy as well."

FMT could possibly be effective if performed "the same way that we would test a drug, which is to put it on top of these normal interventions," he said, adding that he wouldn't expect a weight-loss benefit from FMT "if it's just alone with nothing, in terms of affecting weight or affecting diabetes."

But, Zarrinpar said, "is there still potential there? Maybe."

He further noted that while the studies show that FMT does change the microbiome in some way, the question remains whether the right bacteria are being changed.

"So much of digestion occurs in the small intestine, and what we are giving these patients is essentially the bacteria that is in the large intestine," Zarrinpar said. "Can we better select what is being transplanted?"

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