Fecal transplants have emerged as a potential treatment for a wide range of conditions, including irritable bowel syndrome, diabetes, and even depression. These so-called poop transplants have understandably received a lot of attention, but new research casts a bit of a wet blanket over the practice.

The procedure involves taking microbes from the poop of a healthy person and transferring them into a patient’s colon. This should restore balance to their gut microbiome, but according to a study published June 6 in the journal Cell, transplanted microbes may colonize the wrong parts of the digestive system. This can result in long-lasting unintended health consequences, the researchers warn.

“I think it’s a bit of a wakeup call to the field that maybe we shouldn’t willy-nilly put large bowel microbes into different parts of the intestine that shouldn’t be there,” said lead author Orlando “Landon” DeLeon, a postdoctoral researcher at the University of Chicago, in a statement.

DeLeon led a team of researchers through a series of experiments on mice to determine how fecal matter transplants affect different parts of the intestine. The mice were separated into three groups. One received microbes from the jejunum (the middle part of the small intestine), the second received microbes from the cecum (a pouch that connects the small intestine to the colon), and the third received a standard fecal transplant from the colon.

Each part of the digestive system contains uniquely adapted microbiota. The researchers wanted to see if the microbes would stick to their respective niches once inside the mice. In fact, they found that each of the transplants successfully colonized the full intestinal tract, creating regional gut “mismatches” that lasted for up to three months after the procedure. 

Microbes that colonized parts of the gut where they didn’t belong triggered metabolic changes in these intestinal regions, with the potential to affect a patient’s health and behavior. The researchers observed changes in the mice’s eating habits, activity, and energy expenditure following the transplants. They also documented changes in gene activity associated with immune function, which in turn led to changes in liver metabolism. Most surprising was the manner in which these foreign microbes altered gene and protein expression in the intestinal lining to make the mismatched gut region more suitable for them.

“It’s like they’re engineering or terraforming their environments to help them fit in,” DeLeon said.

To determine whether these mismatches could occur in actual fecal transplant patients, he and his colleagues conducted additional tests using human tissue samples. Results showed that transplanted gut bacteria can colonize parts of the human digestive system where they don’t naturally belong.

“If we’re designing good therapeutics, we should be aware of the importance of matching the regional microbiota to their proper environments, so that we provide better overall health benefits,” DeLeon said. For example, the findings suggest it may be safer to use microbes retrieved from all the parts of the digestive system, according to the researchers.

The Food and Drug Administration (FDA) only recommends fecal transplants for treating repeated infections of Clostridium difficile, or C. diff. This bacterium—which can cause severe gastrointestinal symptoms—most commonly sickens hospital patients who have been treated with antibiotics. Fecal transplants have proven to be highly effective for treating these infections, and those results have encouraged researchers to investigate other applications for this procedure. 

A wave of new research suggests that fecal transplants could treat conditions that go beyond the gut. Indeed, studies have found that this procedure could benefit patients with neurodevelopmental and psychiatric disorders, multiple sclerosis, type 2 diabetes, and more. 

DeLeon’s findings suggest that doctors need to better understand the risks of fecal matter transplants before this treatment can be used for diseases other than C. diff. He plans to keep investigating how different microbes affect each part of the intestine and explore ways to restore altered regions to their original state. 

This study shows that when it comes to gut microbes, location really matters. Getting the right bugs in the right place could unlock the full potential of fecal transplants.