biostudies-literatureBurgueno JFNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSCedars-Sinai Medical Center101694https://www.ebi.ac.uk/biostudies/studies/S-EPMC12865638biostudies-literatureUnknown20(4)<h4>Background & aims</h4>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.<h4>Methods</h4>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 wCellular and molecular gastroenterology and hepatologyLocal Interactions Between Innate Immune Signaling, Microbiota, and Bile Acids Drive the Development of Duodenal Adenomas.PMC12865638R01DK099076R01 DK099076Brito NSantander AMFernandez IGonzalez EEBan YJacobsen GEWilson LBarnes SPignac-Kobinger JBurgueno JFWang LHazime HSundrud MSFritsch JCickovski TGao ZAbreu MTDione HDfalseLocal Interactions Between Innate Immune Signaling, Microbiota, and Bile Acids Drive the Development of Duodenal Adenomas.<h4>Background & aims</h4>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.<h4>Methods</h4>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 w2025-01-01T00:00:00Z2025 Dec2026-07-05T03:13:14.634Z2026-07-05T03:11:42.54ZS-EPMC128656384134443910.1016/j.jcmgh.2025.101694