By
Matt Wood
Director of Communications, Biological Sciences Division
The gut microbiome impacts our health in many ways, one of which is by consuming, producing or modifying metabolites—small molecules like amino acids, sugars, and fatty acids that are found in foods or are the byproducts of cellular activities. Metabolites in the gut reflect the activity of microbes, host cells, and tissues and can serve as biomarkers for disease.
Sam Light, PhD, Assistant Professor of Microbiology at the University of Chicago, studies the different types of metabolisms that gut bacteria use to produce energy, such as fermentation and respiration. Understanding these processes can help scientists learn how different kinds of bacteria colonize the gut, what chemicals and nutrients they metabolize, and how this affects the health of the host.
During a recent research project, published in Cell Host & Microbe, Light and his team screened gut microbiome samples from human donors to see how they metabolized a variety of compounds, including steroid hormones. These include a wide variety of molecules that play crucial roles in the body. Glucocorticoids, like cortisol, help regulate inflammation, immune response, and metabolism; sex steroids, like estrogen, androgen, and progestin, of course, play a vital role in reproduction and sexual functions. Since steroid hormones can have such powerful biological effects, there is ongoing interest in learning more about how the body processes them. Both natural and synthetic versions of steroids are also used to treat autoimmune diseases, hormone deficiencies, and some cancers.
As Light’s team studied how gut microbes responded to the presence of different metabolites, they discovered a new bacterial species that was particularly adept at inactivating cortisol (and then aptly named it Clostridium steroidoreducens). They further identified the genes the bacteria were using to break down steroids and found these same genes in other prominent gut bacteria, such as Ruminococcus gnavus, giving them steroid inactivating abilities as well.
Since steroids play an important role in managing inflammation in the gut, the researchers next wanted to see the prevalence of this kind of genetic activity in microbiome samples from human patients. Some of the samples they tested were from patients with active Crohn’s disease, a type of inflammatory bowel disease that causes inflammation in the small intestines. They saw higher levels of steroid-inactivating genes in these patients, suggesting that in patients suffering from a flare up of Crohn’s disease, the bacteria were actively breaking down steroids that could help keep inflammation in check.
“You could imagine a mechanism like this where the body makes the glucocorticoids to prevent the flare from happening, but if you have too much of this microbe around it inactivates the steroid and promotes the flares,” Light said. “Or alternatively, maybe the flare happens, and then this microbe expands under conditions that are favorable for its growth and prolongs inflammation."
Light’s team also saw evidence that these same bacteria can inactivate synthetic glucocorticoids like prednisolone that are used to treat inflammatory bowel diseases, reducing their effective dose in mice and potentially impacting effectiveness in human patients too. While Light says there is still a lot of work to do to see how this chain of events plays out in people, it’s another fascinating look at the impact gut microbes have on our bodies.
“I think the question about whether microbes that thrive under inflammatory conditions are using this pathway to inactivate a built-in circuit for managing inflammation is really interesting,” Light said. “There could be other ways that microbes modify steroid hormones that impact their efficacy. So, we’re interested in exploring more ways microbes do these things to contribute to or protect against inflammatory disease.”
