Glucocorticoid-induced changes of the gut microbiota and metabolic markers in healthy young men: Outcome of a randomized controlled trial

Glucocorticoids induce insulin resistance and suppress immunity, but their impact on gut microbiota, which may modulate metabolism and immunity remains under explored. In this 7-day trial, we assess 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 reveal that PO glucocorticoid causes 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 alters microbial pathways and enzymes related to glycolysis and lipid metabolism, with changes in predicted metabolites such as hypoxanthine and phenylacetate. IM treatment results 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. The trial was approved by the Danish Medicine Agency (EudraCT protocol number: 2016-001850-16).