Oral administration of antibiotics results in fecal occult bleeding due to metabolic disorders and defective proliferation of the gut epithelial cell in mice
Oral administration of antibiotics results in fecal occult bleeding due to metabolic disorders and defective proliferation of the gut epithelial cell in mice
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DOI：
10.1111/gtc.12649
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发表时间：
2018-11
期刊：
影响因子：
2.1
通讯作者：
A. Sonoda;Naganori Kamiyama;Sotaro Ozaka;Y. Gendo;T. Ozaki;Haruna Hirose;K. Noguchi;Benjawan Saechue-Benja
中科院分区：
文献类型：
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作者：
A. Sonoda;Naganori Kamiyama;Sotaro Ozaka;Y. Gendo;T. Ozaki;Haruna Hirose;K. Noguchi;Benjawan Saechue-Benja
抗生素有时会对结肠炎的发病机制产生不利影响，这是由于肠道内稳态的破坏导致的生态失调。然而，抗生素诱导的结肠炎的致结肠炎作用的确切机制在很大程度上是未知的。在这里，我们展示了一种由氨苄青霉素和万古霉素联合治疗诱导的新型小鼠粪便隐匿性出血模型，其伴随着盲肠扩大，促炎细胞因子IL-6和IL-12上调，Ki-67阳性上皮细胞数量减少和结肠中凋亡细胞数量增加。此外，气相色谱-串联质谱分析表明，各种代谢产物，包括谷氨酸和丁酸，盲肠内容物显着减少。此外，在扩大的盲肠中，丁酸生产梭菌的丰度显著降低。有趣的是，补充谷氨酸或其前体谷氨酰胺抑制结肠IL-6和IL-12，保护细胞凋亡并防止粪便潜血，表明谷氨酸水平降低是抗生素诱导的粪便潜血的可能机制。我们的数据显示了抗生素诱导的粪便隐匿性出血的新机制，为谷氨酸治疗抗生素诱导的结肠炎的临床应用提供了新的见解。
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.