Work

Tryptophan Indole Metabolites Reduce Anastomotic Leakage Through Aryl Hydrocarbon Receptor-Driven Interleukin-22 Production

Year: 2026

Type: article

Abstract: BACKGROUND & AIMS: Colorectal cancer (CRC) often requires surgical resection of the tumor and an anastomosis. Anastomotic leakage (AL) occurs in 2.8% to 30% of patients, which increases postoperative morbidity and complications. The preoperative microbiome composition is implicated in AL. Recent studies have shown that microbial tryptophan (Trp) metabolism into aryl hydrocarbon receptor (AhR) indole-derivatives contributes to intestinal tissue healing. Here, we addressed the role of Trp and its metabolites in AL in a CRC patient cohort and a colon-anastomosis mouse model. METHODS: , and interleukin (IL)-22 drug-targeting to evaluate the role of AhR and IL-22 in AL. RESULTS: mice. AhR agonism failed to rescue healing under IL-22 deficiency. Furthermore, low-Trp diet-fed WT mice exhibited reduced fecal concentration of AhR agonists, AhR-agonist producing bacteria, and augmented AL. This phenotype was prevented by dietary supplementation with the AhR agonist indole-3-carbinol. CONCLUSIONS: Stimulation of the AhR/IL-22 by synthetic agonists or dietary-derived Trp-metabolites can prevent AL.

Source: Cellular and Molecular Gastroenterology and Hepatology

DOI: 10.1016/j.jcmgh.2026.101756