Dual Deficiency of IL4I1 and LAO1 Promotes Inflammatory Diarrhea via Disruption of L-Amino Acid Metabolism and the IDO1-Kynurenine Pathway

Furthermore, 16S rRNA gene sequencing revealed altered beta diversity and reduced abundance of Short-chain fatty acid-producing bacteria in DKO mice. Among short-chain fatty acids, pentanoate was significantly decreased in DKO cecal contents. Collectively, these findings suggest that IL4I1 and LAO1 are essential for maintaining intestinal immune and metabolic balance.

Their combined deficiency disrupts L-amino acid metabolism and H₂O₂-mediated regulation of the IDO1–kynurenine pathway, ultimately promoting gut dysbiosis and inflammatory diarrhea. This study provides novel insights into the metabolic and microbial mechanisms underlying colonic inflammation and highlights IL4I1 and LAO1 as potential targets for therapeutic intervention in inflammatory bowel diseases. This study provides novel insights into the metabolic and microbial mechanisms underlying colonic inflammation and highlights IL4I1 and LAO1 as potential targets for therapeutic intervention in inflammatory bowel diseases.