Seeking an Obesity Cure, Researchers Turn to the Gut Microbiome

In at least one case described in a medical journal, a lean woman who received a fecal transplant from her overweight daughter to treat a C. diff infection quickly gained 34 pounds. Her doctors, however, said they could not be sure that the transplant fueled her sudden weight gain.

Dr. Purna Kashyap, head of the Gut Microbiome Laboratory at the Mayo Clinic, said that treating C. diff with a fecal transplant makes perfect sense because it dislodges a harmful pathogen and restores equilibrium to the gut. But obesity and metabolic disease are far more complex, driven by an array of factors, including genetics, diet, environment and lifestyle. The idea that a single intervention, a transplant of a new community of microbes, could effectively treat obesity is unrealistic, he said.

“The logic behind it falls apart,” he added. “It’s saying, because I don’t know what’s going on, let me just treat it with everything that I have and hope for the best.”

Some researchers nonetheless wondered what would happen if obese patients were given the gut microbes of slender people. The first direct test of this came in 2012. Dutch researchers showed that transferring a lean donor’s microbiota to the guts of obese men with metabolic syndrome led to a sharp increase in the recipients’ insulin sensitivity and their microbial diversity after six weeks, suggesting that the transplants influenced their metabolisms.

At Mass General, Dr. Yu and her colleagues recruited 24 obese men and women with insulin resistance, along with four lean donors. The donors were screened for an array of medical conditions to ensure that they were healthy and would not transmit any infections to the recipients. The researchers selected donors who had a history of always being very lean: Their ideal candidates were people who said they could eat whatever they wanted and still remain skinny.

“There could be many reasons why those people are special,” Dr. Yu said of the donors. “There could be genetic reasons that are unrelated to the microbiome. But we had to start somewhere.”

Half the obese subjects took specially prepared frozen capsules containing stool from the donors on a weekly basis, while the others received a placebo. After 12 weeks, the researchers found that the fecal treatment was safe and tolerable and that the subjects had acquired microbiota that resembled that of their skinny donors. But over all, unlike in the Dutch study, there was no improvement in their metabolic health. Like much of the microbiome research to date, both trials were small and exploratory and did not reach definitive conclusions.

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