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In search of a cure for obesity, researchers look to the gut microbiome

In at least one case described in a medical journal, a skinny 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 couldn’t be sure the transplant fueled her sudden weight gain.

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

“The logic behind this is collapsing,” he added. “That is to say, because I don’t know what’s going on, just let me deal with it with everything I have and hope for the best.”

However, some researchers have wondered what would happen if obese patients received gut microbes from thin people. The first direct test took place in 2012. Dutch researchers have shown that the transfer of microbiota from a lean donor into the bowels of obese men with metabolic syndrome resulted in a sharp increase in the insulin sensitivity of the recipients and of their microbial diversity after six weeks, suggesting that the transplants influenced their metabolism.

At Mass General, Dr Yu and his colleagues recruited 24 obese men and women with insulin resistance, as well as four lean donors. The donors were screened for a range of medical conditions to make sure they were in good health and would not pass any infections on to the recipients. The researchers selected donors who had always been very skinny: their ideal candidates were people who said they could eat whatever they wanted and still stay skinny.

“There could be many reasons why these people are special,” Dr Yu said of the donors. “There could be genetic reasons that are not related to the microbiome. But we had to start somewhere.

Half of the obese subjects took specially prepared frozen capsules containing donor stool on a weekly basis, while the rest received a placebo. After 12 weeks, the researchers found that the fecal treatment was safe and tolerable and that the subjects had acquired a microbiota that resembled that of their lean donors. But overall, unlike 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 come to definitive conclusions.

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