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

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 antibiotics-induced colitis are largely unknown. Here we demonstrate a novel murine fecal occult bleeding model induced by the combinatorial treatment of ampicillin and vancomycin， which is accompanied by an enlarged caecum， the presence of fecal occult blood， 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 revealed that various kinds of metabolites， including glutamic acid and butyric acid， were significantly decreased in the caecal contents. In addition， abundance of butyric acid producer Clostridiales was dramatically reduced in the enlarged caecum. 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 antibiotics-induced fecal occult bleeding. Our data demonstrated a novel mechanism of antibiotics-induced fecal occult bleeding providing a new insight into the clinical application of glutamic acid for the treatment of antibiotics-induced colitis. This article is protected by copyright. All rights reserved.