著者

Mohammad Ibrahim QASIMI Susumu FUKUZAWA Ken SUENAGA Jun KAMBE Chunmei LI Shozo TOMONAGA Takahiro KAWASE Takamitsu TSUKAHARA Kazuhiko HIRAYAMA Ryo INOUE Yuki YAMAMOTO Kentaro NAGAOKA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.23-0080, (Released:2023-05-03)

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L-amino acid oxidase (LAAO) is a metabolic enzyme that converts L-amino acids into ketoacids, ammonia, and hydrogen peroxide (H2O2). The generated H2O2 has previously been shown to have antibacterial and gut microbiota-modulatory properties in LAO1 knock-out (KO) mice. Since most microbial metabolites reach the liver through the portal vein, we examined gut-liver interactions in LAO1 KO mice. We found lower total cholesterol levels, higher glutamic pyruvic transaminase (GPT) levels in the serum, and higher pro-inflammatory cytokine mRNA expression in the liver tissue. In wild-type (WT) mice, LAO1 was expressed in gut tissues (ileum and colon). Microbiome analysis revealed that the abundance of some bacteria was altered in LAO1 KO mice. However, short-chain fatty acid (SCFAs) levels in cecal feces and gut permeability did not change. Fecal microbiota transplantation (FMT) revealed that feces from LAO1 KO mice slightly stimulated pro-inflammatory cytokine expression in the liver. During metabolomic analysis, 5-Aminolevulinic acid (5-ALA) was the only metabolite found to be significantly upregulated in the portal and abdominal veins of the LAO1 KO mice. Intraperitoneal administration of 5-ALA to WT mice significantly increased IL-6 mRNA expression in the liver. These observations suggest that gut LAO1 plays a role in regulating 5-ALA production and that a high level of 5-ALA stimulates the liver to increase pro-inflammatory cytokine expression by disrupting LAO1 in mice.