Oral administration of antibiotics results in fecal occult bleeding due to metabolic disorders and defective proliferation of the gut epithelial cell in mice

作者：Akira Sonoda, Naganori Kamiyama, Sotaro Ozaka, Yoshiko Gendo, Takashi Ozaki, Haruna Hirose, Kaori Noguchi, Benjawan Saechue, Nozomi Sachi, Kumiko Sakai, Kazuhiro Mizukami, Shinya Hidano, Kazunari Murakami, Takashi Kobayashi · 发表于：Genes to Cells · 年份：2018 · DOI：10.1111/gtc.12649 · 被引用次数：16 · 研究领域：Clostridium difficile and Clostridium perfringens research、Gut microbiota and health、Helicobacter pylori-related gastroenterology studies

Antibiotics sometimes exert adverse effects on the pathogenesis of colitis due to the dysbiosis resulting from the disruption of gut homeostasis. However, the precise mechanisms underlying colitogenic effects of antibiotic-induced colitis are largely unknown. Here, we show a novel murine fecal occult bleeding model induced by the combinatorial treatment of ampicillin and vancomycin, which is accompanied by an enlarged cecum, upregulation of pro-inflammatory cytokines IL-6 and IL-12, a reduction in Ki-67-positive epithelial cell number and an increase in the apoptotic cell number in the colon. Moreover, gas chromatography-tandem mass analysis showed that various kinds of metabolites, including glutamic acid and butyric acid, were significantly decreased in the cecal contents. In addition, abundance of butyric acid producer Clostridiales was dramatically reduced in the enlarged cecum. Interestingly, supplementation of monosodium glutamate or its precursor glutamine suppressed colonic IL-6 and IL-12, protected from cell apoptosis and prevented fecal occult blood indicating that the reduced level of glutamic acid is a possible mechanism of antibiotic-induced fecal occult bleeding. Our data showed a novel mechanism of antibiotic-induced fecal occult bleeding providing a new insight into the clinical application of glutamic acid for the treatment of antibiotic-induced colitis.