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).
Authors
- Marc Clos‐Garcia (ORCID: https://orcid.org/0000-0002-0208-1372)
- Evelina Stankevič (ORCID: https://orcid.org/0000-0002-6433-6975)
- Asger Lund (ORCID: https://orcid.org/0000-0003-1212-3764)
- Henrik Vestergaard (ORCID: https://orcid.org/0000-0003-3090-269X)
- Thomas Bryrup (ORCID: https://orcid.org/0000-0001-8533-6766)
- Oluf Pedersen (ORCID: https://orcid.org/0000-0002-3321-3972)
- Yong Fan (ORCID: https://orcid.org/0000-0003-4813-7017)
- Markus Eiken
- Niklas Rye Jørgensen (ORCID: https://orcid.org/0000-0001-9624-5210)
- Liwei Lyu (ORCID: https://orcid.org/0000-0002-7387-8557)
- Filip K. Knop (ORCID: https://orcid.org/0000-0002-2495-5034)
- Susanne Brix (ORCID: https://orcid.org/0000-0001-8951-6705)
- Tue H. Hansen (ORCID: https://orcid.org/0000-0001-5948-8993)
- Torben Hansen (ORCID: https://orcid.org/0000-0001-8748-3831)
- Trine Rune Høgh Nielsen
Institutions
- University of Copenhagen (DK)
- Novo Nordisk Foundation (DK)
- Glostrup Hospital (DK)
- Gentofte Hospital (DK)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102426
- Citations
- 1
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Lundbeckfonden
- Novo Nordisk
- Copenhagen Graduate School for Nanoscience and Nanotechnology
- Novo Nordisk Fonden
- Novo Nordisk Foundation Center for Basic Metabolic Research
- H. Lundbeck A/S