biostudies-literatureVerna GNIDDK NIH HHSNIDDKe196712https://www.ebi.ac.uk/biostudies/studies/S-EPMC12721895biostudies-literatureUnknown136(1)Colitis-associated cancer (CAC) arises from a complex interplay between host and environmental factors. In this report, we investigated the role of the gut microbiome using Winnie mice, an ulcerative colitis-like (UC-like) model with a missense mutation in the Muc2 gene. Upon rederivation from a conventional (CONV) to a specific pathogen-free (SPF) facility, Winnie mice developed severe colitis and, notably, spontaneous CAC that progressively worsened over time. In contrast, CONV Winnie mice showed only mild colitis but no tumorigenesis. By comparison, when re-derived into germ-free (GF) conditions, SPF Winnie mice were protected from colitis and colon tumors, indicating an essential role for the gut microbiome in the development of CAC in these mice. Using shotgun metagenomics, metabolomiThe Journal of clinical investigationA missense mutation in Muc2 promotes gut microbiome and metabolome-dependent colitis-associated tumorigenesis.PMC12721895DK042191R56 DK042191R56 DK055812R37 DK042191DK019222R01 DK055812R01 DK042191DK055812Miller ENPizarro TTChieppa MIslam BNZhang LDe Almeida Celio FCominelli FSommella EMVerna GLicastro DMerciai FXin WDe Santis SCaponigro VCampiglia PfalseA missense mutation in Muc2 promotes gut microbiome and metabolome-dependent colitis-associated tumorigenesis.Colitis-associated cancer (CAC) arises from a complex interplay between host and environmental factors. In this report, we investigated the role of the gut microbiome using Winnie mice, an ulcerative colitis-like (UC-like) model with a missense mutation in the Muc2 gene. Upon rederivation from a conventional (CONV) to a specific pathogen-free (SPF) facility, Winnie mice developed severe colitis and, notably, spontaneous CAC that progressively worsened over time. In contrast, CONV Winnie mice showed only mild colitis but no tumorigenesis. By comparison, when re-derived into germ-free (GF) conditions, SPF Winnie mice were protected from colitis and colon tumors, indicating an essential role for the gut microbiome in the development of CAC in these mice. Using shotgun metagenomics, metabolomi2026-01-01T00:00:00Z2026 Jan2026-07-15T09:17:53.331Z2026-07-02T03:08:59.404ZS-EPMC127218954119665810.1172/JCI196712