Glucocorticoids, which are widely prescribed for inflammation and immune conditions, are known to influence blood sugar and immune responses. Now, researchers have found that even short-term glucocorticoid use can reshape the gut microbiota, changing specific bacteria and their metabolic activity.

The findings, published in Cell Reports Medicine, suggest that glucocorticoids can alter metabolic and immune regulation by reshaping gut microbial functions.

Glucocorticoid hormones, a type of steroid hormones, help regulate metabolism, immunity, stress, and other processes, but too much can cause insulin resistance, increased infection risk, bone loss, and metabolic disruptions. Previous research suggests that glucocorticoids may alter the gut microbiota, which influences metabolism and immune health, but it remains unclear whether these changes come from direct effects on gut bacteria.

So, researchers led by Liwei Lyu at Herlev-Gentofte University Hospital in Denmark set up a clinical trial to study how glucocorticoids affected the gut microbiota, metabolism, and immunity in healthy young men.

Glucocorticoid treatment 

For seven days, study participants received either oral or injected glucocorticoids or no treatment. Glucocorticoid treatment was well tolerated with no major side effects reported. While overall blood sugar levels didn’t change, people who received oral glucocorticoids had lower inflammation markers and higher insulin levels.

Oral glucocorticoid treatment also resulted in signs of reduced insulin sensitivity, meaning the body had to produce more insulin to manage the same amount of sugar. 

These changes were linked to increased levels of bacteria such as Turicibacter bilis, Blautia, and Collinsella as well as lower levels of Sutterella wadsworthensis, Dysosmobacter welbionis, and several Clostridium and Lachnospira species. People who received injected glucocorticoids showed fewer changes, the researchers found. 

Altering metabolism

In people who received oral glucocorticoids, microbial pathways involved in breaking down sugars and fats were more active, suggesting that these bacteria may process glucose and lipids differently. Some amino acid and vitamin-related pathways were also affected. 

Using computer models, the researchers predicted that oral glucocorticoids increase the levels of certain microbial metabolites that reduce inflammation. Injected glucocorticoids had smaller effects and mostly influenced sugar-processing pathways. 

The findings indicate that glucocorticoids can alter gut microbial metabolism in ways that may influence the body’s metabolic and immune functions, the authors say. “Overall, the outcome of the present clinically controlled trial highlights the nuanced relationship between glucocorticoid therapy, gut microbiota, and host metabolic and systemic immune responses.”