Clemson research could lead to improved treatment for C. diff and other GI illnesses

Antibiotics have turned once life-threatening diseases into easily treatable illnesses. Sometimes, however, they can lead to other problems.

The human gastrointestinal tract has an “ecosystem” of thousands of bacteria and other organisms, and many of them help keep people healthy. Taking antibiotics can kill “good” bacteria along with the bad, allowing an overgrowth of opportunistic, disease-causing bacteria such as Clostridioides difficile. 

Commonly called C. diff, the bacteria produce toxins that attack and destroy the lining of the gut and cause diarrhea, stomach cramps and dehydration, and in the worst cases, life-threatening inflammation of the colon. Since antibiotics are the primary initial treatment for C. diff, recurrent infections can be a major challenge.

An effective treatment option for many patients — but not all — with recurrent C. diff infections is fecal microbiota transplantation, where stool from a healthy donor is put into the colon of the patient to balance the gut microbiome. 

Works for some, not others

Two researchers at Clemson University — Anna Seekatz, an assistant professor in the Department of Biological Sciences, and Sophie Millard, a Ph.D. candidate in Seekatz’s lab — are working to understand why FMT works in some people and not others.

Their research, published in the journal mBio, revealed that the effectiveness of FMT may be compromised by a mismatch between donor microbes and the recipient environment, leading to deficits in key microbial metabolites.

“One of our most surprising findings is that just because microbes successfully take hold in the gut doesn’t mean they’ll behave the way we expect them to,” Millard said. “A microbe might ‘move in,’ but that doesn’t guarantee it will do the job it’s supposed to.”

That finding suggests there are other factors that need to be considered, Seekatz said.

“Some of those factors could be microbial cooperation, or how well the microbes that remain in the gut during disease are interacting with the microbes you’re inputting as part of the FMT, or maybe there’s a host involvement in getting the microbes to act,” she said. “When we’re looking at these microbiome studies, sometimes we’re just looking at who is there. But that’s not enough. We have to look at what they’re doing to understand the total context of what’s going on.”

Within a recurrent C. diff mouse model Seekatz developed while a postdoctoral fellow at the University of Michigan, mice with C. diff that were given stool from a healthy mouse cleared C. diff pretty rapidly. But if the sick mouse was given healthy human poop, C. diff wasn’t cleared.

“Ecologists would say that this makes sense because our microbes are different. But if you actually look at the microbiome community that was transplanting, we saw that these human microbes were transplanting in the gut. They were there. But they weren’t clearing C. diff,” Seekatz said.

Genes not behaving like they should

Further testing showed the microbes had the genes and functional potential to clear C. diff, but they weren’t behaving the way they should be. Seekatz said that could be because of microbial cooperation is missing or because of host involvement in getting the microbes to behave or function properly.

“This matters because many microbial therapies are considered successful if the bacteria can colonize, but if they’re not actually performing the right functions, the treatment might not work as intended,” Millard said.

Seekatz said the study is relevant for human disease because healthy human microbiomes vary person to person based on geography, genetics and life events.

“By understanding how the microbes are actually working together, whether it be in the donor-recipient relationship or with the host, maybe we can make this more effective than a one-size-fits-all treatment because here is still a subset of individuals who fail even with FMT,” she said. “A lot of our focus has been on identifying a sort of magic mixture of microbes that might work.”

Millard said the research helps move closer to more precise and effective microbiome-based treatments. 

“Instead of relying on whole stool transplants, the goal is to develop targeted therapies made up of specific microbes that not only colonize the gut but also perform the functions needed to support health,” she said. “By understanding what influences both microbial colonization and function, we can design safer, more reliable treatments for C. diff and potentially other gut-related conditions.”