Work

Local Interactions Between Innate Immune Signaling, Microbiota, and Bile Acids Drive the Development of Duodenal Adenomas

Year: 2025

Type: article

Abstract: BACKGROUND & AIMS: Duodenal adenomas have malignant potential, yet the drivers of duodenal tumorigenesis remain unclear. Duodenal adenomas robustly develop in villin- Toll-like receptor 4 (TLR4) mice, a transgenic mouse model of increased innate immune signaling in the intestinal epithelium. Here, we sought to test the contributions of the microbiota and bile acids to duodenal adenoma development. METHODS: Duodenal tissue was analyzed for proliferation rate and histology in villin-TLR4 vs wild-type mice. Mice were rederived into germ-free conditions and administered a diet containing the bile acid sequestering resin cholestyramine or treated with the NADPH oxidase inhibitor apocynin. Chemokine expression and myeloid cell recruitment were measured. Findings from mouse studies were corroborated by RNA sequencing and tissue microarray analyses of human duodenal adenomas. RESULTS: myeloid cells. CONCLUSIONS: Bile acids and the microbiota are necessary for duodenal adenoma development and are potentially modifiable risk factors in humans at risk of duodenal adenomas. The recruitment of myeloid cells may promote tumor progression via the release of reactive oxygen species.

Source: Cellular and Molecular Gastroenterology and Hepatology

DOI: 10.1016/j.jcmgh.2025.101694