GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300955/primary200OKTranscriptomicsMus musculusExpression profiling by arrayhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300955GEOGSEfalseDual Deficiency of IL4I1 and LAO1 Promotes Inflammatory Diarrhea via Disruption of L-Amino Acid Metabolism and the IDO1-Kynurenine PathwayThe oxidoreductases interleukin 4-induced gene 1 (IL4I1) and L-Amino acid oxidase 1 (LAO) are known to catalyze L-amino acid metabolism, yet their physiological roles in intestinal homeostasis remain largely unexplored. In this study, we investigated the impact of IL4I1 and LAO1 deficiency on colonic inflammation by generating wild-type, single knockout (IL4I1 KO and LAO1 KO), and double knockout (DKO) mice. Notably, DKO mice exhibited spontaneous diarrhea and histologically confirmed colitis, which were absent or rare in the other genotypes. Transcriptomic profiling and qRT-PCR analyses revealed upregulated expression of pro-inflammatory cytokines (IL-6, IL-17, IFN-γ) and Th1/Th17 transcription factors, along with overexpression of indoleamine 2,3-dioxygenase 1 (IDO1) in the colon of DKO mice. Metabolomic analysis indicated elevated colonic kynurenine levels and impaired metabolism of L-phenylalanine, L-tyrosine, and L-tryptophan. These changes were associated with a significant reduction in hydrogen peroxide (H₂O₂) production. 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.2026/06/28GSE300955GSM9072666GSM9072665GSM9072664GSM9072663GSM9072659GSM9072669GSM9072668GSM9072667GSM9072662GSM9072661GSM9072660GSM907267023038300955Mus musculus