Dysbiotic microbiota trigger colitis-associated colorectal cancer and imprint a distinctive bile acid profile in a PSC-IBD model - PubMed
6 hours ago
- #microbiome
- #bile acid
- #colorectal cancer
- PSC-UC (Primary Sclerosing Cholangitis-associated Ulcerative Colitis) shows higher inflammatory activity and right-shifted dysplasia burden compared to UC-only.
- Dysbiotic microbiota in PSC-UC trigger colitis-associated colorectal cancer and are linked to secondary bile acid (BA) deficiency.
- Germ-free (GF) DKO mice were protected from colitis and dysplasia, but live donor fecal microbiota transplantation (FMT) reinstated severe colitis and dysplasia.
- IL-10-/- donor FMT or cohousing attenuated colitis and increased secondary BA levels, while wild-type/MDR2-/- donor transfers were non-colitogenic.
- Direct deoxycholic acid repletion in GF DKO mice caused hepatotoxicity, suggesting controlled restoration of BA-transforming microbial functions is a better approach than indiscriminate BA replacement.