Gut microbiota derived indole-3-acetic acid ameliorates precancerous inflammatory intestinal milieu to inhibit tumorigenesis through IL-35

• 31 March 2026

Abstract
Background Gut microbiota can significantly alter the risk or progression of cancer by maintaining gut immune
system homeostasis. However, the exact mechanism by which the gut microbiota and its metabolites influence
colorectal tumorigenesis is unclear. Methods The roles of tryptophan metabolite indole-3-acetic acid (IAA) in inflammation and tumor development were investigated in dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS mouse models with or without IAA supplementation and with or without Lactobacillus reuteri-produced IAA. Pregnane X receptor (PXR) knockout (KO) mice and aryl hydrocarbon receptor KO mice were used to explore the mechanism by which IAA regulates
interleukin (IL)-35 expression. IL-35+immune cells were stimulated in vitro and analyzed by flow cytometry.
Additionally, metabolites were analyzed by liquid chromatography-mass spectrometry

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