Inflammatory bowel disease, or IBD, is a long-term condition that causes inflammation of the digestive tract and can make people respond differently to medications, including commonly used steroid therapies. Researchers have now found that a gut bacterium, Clostridium steroidoreducens, can chemically modify steroid hormones, including those used to treat IBD. 

The findings, published in Cell Host & Microbe, suggest that certain gut microbes could influence the effectiveness of steroid treatments, offering new insights into why some people experience reduced responses to IBD drugs.

Gut bacteria are known to influence hormone levels and drug metabolism, but it was unclear which specific gut microbes can directly modify steroid hormones and whether they could reduce the effectiveness of steroid therapies for IBD.

So, Christian Jacoby at the University of Chicago in Illinois and his colleagues took stool samples from a healthy human donor with no history of inflammatory disease and screened their gut bacteria for the ability to metabolize steroid hormones.

Steroid metabolism 

The researchers discovered that the gut bacterium Clostridium steroidoreducens can break down natural steroids, such as cortisol, as well as synthetic drugs, including prednisolone—a commonly used glucocorticoid to treat IBD.

By analyzing gene expression in C. steroidoreducens bacteria grown with cortisol, the team discovered an enzyme pathway, called OsrABC, that is responsible for its breakdown. They found that three genes—OsrB, OsrC, and OsrA—are induced by steroid exposure. These genes code for enzymes that work sequentially to convert natural and synthetic steroid hormones into inactive derivatives. 

An analysis of human fecal samples revealed that OsrB homologs are present in nearly all individuals, whereas OsrA is less common but enriched in people with Crohn’s disease, a type of IBD. People undergoing glucocorticoid therapy had higher levels of OsrA-carrying bacteria, the researchers found. 

Therapeutic strategies 

To test the effects of C. steroidoreducens on drug bioavailability, the researchers colonized germ-free mice with the microbe and administered oral prednisolone. They found that bacterial colonization reduced drug levels in the lower intestine and bloodstream.

The findings highlight a previously underappreciated factor in steroid resistance among people with IBD, the researchers say. “The ability of gut bacteria to inactivate glucocorticoids may not only impact endogenous hormone signaling but also compromise the efficacy of steroid-based treatments in IBD,” the authors say.

“Future research should determine the extent to which microbial transformations contribute to steroid resistance and explore therapeutic strategies to prevent glucocorticoid degradation in IBD patients.”