A study warns of the possible risks of fecal transplants

Fecal microbiota transplants (FMTs) have been proposed as a treatment for a variety of diseases—from inflammatory bowel disease, obesity, type 2 diabetes, to autism. However, new research from the University of Chicago cautions against their widespread use, due to the risk of long-lasting and unexpected side effects for recipients.

FMT involves transferring microbes present in the feces of a healthy person to a sick person, in the hopes of restoring balance to the gut microbiota. However, because these feces contain primarily anaerobic colon microbes (those that cannot tolerate oxygen), the procedure can cause imbalances if those bacteria end up colonizing other parts of the gut, such as the small intestine.

In studies with mice and human samples, researchers observed that these anaerobic bacteria not only colonized the small intestine after a single transplant, but also remained there for months. They also modified the intestinal environment in their favor, altering the recipient's metabolism, behavior, and energy balance.

"This finding should make us rethink how we use FM," explains Orlando DeLeon, senior author of the study. "If we want effective therapies, we need to ensure the microbes are introduced into the correct intestinal environment."

FMT is only approved in some countries for recurrent infections with Clostridium difficile (C. diff), a bacterium that causes severe intestinal symptoms. However, its success in these cases has led some doctors to use it for other digestive diseases.

The problem is that the gut isn't a uniform environment : it has very different regions, each with its own specialized microbial ecosystem. Replacing the microbiota in one area doesn't necessarily fix the rest of the system.

To study this, the team transplanted microbes from different areas of the intestine (the jejunum, colon, and cecum) into mice. All managed to colonize regions outside their original location, causing disruptions that lasted up to three months. They also affected the animals' liver metabolism, feeding behavior, and energy expenditure.

One of the most surprising findings was that microbes modified gut tissue to suit their needs, changing the genetic expression of the place they colonized to make it more similar to their native environment.

Eugene B. Chang, co-author of the study, notes that we still don't fully understand the long-term effects of introducing microbes into new gut areas. " We don't really know what's in a FMT, just that it's mixed microbes ," Chang says. "But even a single transplant can permanently change the relationship between host and microbiota."

As an alternative, researchers propose "omni-microbial" transplants (OMT): including microbes from all regions of the gut, not just the colon. This way, when administered (orally or endoscopically), the microbes could settle more naturally in their rightful place.