Tryptophan indole metabolites reduce anastomotic leakage through aryl hydrocarbon receptor-driven interleukin-22 production - PubMed
3 days ago
- #Anastomotic leakage
- #Aryl hydrocarbon receptor
- #Tryptophan metabolism
- Tryptophan indole metabolites reduce anastomotic leakage (AL) by activating the aryl hydrocarbon receptor (AhR) and increasing interleukin-22 (IL-22) production.
- Anastomotic leakage occurs in 2.8-30% of colorectal cancer patients post-surgery, increasing complications.
- Preoperative microbiome composition and microbial tryptophan metabolism influence AL risk.
- Indole-3-acetic acid levels were lower in AL patients compared to those with proper anastomotic healing (AH).
- AhR-deficient mice showed worse AL, reduced IL-22, and fewer IL-22-producing immune cells.
- IL-22 neutralization worsened AL in mice, while IL-22 supplementation improved healing in AhR-deficient mice.
- A low-tryptophan diet reduced AhR agonist production and worsened AL, but supplementation with indole-3-carbinol prevented this.
- AhR/IL-22 stimulation via synthetic agonists or dietary tryptophan metabolites may prevent AL.