Glucocorticoid-induced changes of the gut microbiota

Glucocorticoids are known to induce insulin resistance and suppress immunity, yet their impact on the gut microbiota, which may modulate metabolism and immunity, is underexplored. In this 7-day trial, we assessed glucocorticoid-induced changes in gut microbiota and metabolic markers in 56 healthy men, randomly assigned to three interventions: oral prednisolone (PO group), intramuscular methylprednisolone acetate (IM group), or saline (CTL group). Shotgun metagenomics revealed that PO glucocorticoid treatment caused shifts in bacterial abundance, increasing Blautia and Collinsella, while decreasing Dysosmobacter welbionis and Anaerotignum faecicola, linked with insulin resistance and immunosuppression markers. Additionally, PO treatment altered microbial pathways and enzymes related to glycolysis and lipid metabolism, with changes in predicted metabolites like hypoxanthine and phenylacetate. IM treatment resulted in minimal microbiota changes. These findings underscore the route-dependent effects of glucocorticoids on gut microbiota and their potential impact on host metabolism and immunity.