Glutamine Supplementation Protects against Experimental Antibiotic-associated Diarrhea
首发时间:2019-03-12
Abstract:Diarrhea is a major adverse effect of antibiotic use; however, no known medical regimen is available yet. Glutamine has a pivotal role in intestinal homeostasis, but its implication in antibiotic-associated diarrhea (AAD) remains unclear. Herein we explored the potential of glutamine supplementation in AAD management by using a preclinical mouse model. Data clearly showed that upon clindamycin exposure glutamine store was depleted in colonic mucosa, whereas glutamine supplementation improved several symptoms of experimental AAD. Mechanistically, clindamycin treatment substantially confounded gut microbiota especially in butyrate-producing strains, thereby leads to fecal butyrate deficiency, and in turn increases the body\'s demand for glutamine. Protective effect of glutamine supplementation on AAD may, at least in part, be explained by restoring the intestinal mucosal barrier and facilitating antimicrobial host defense. Taken together, our findings in this study provided a valuable rationale for guiding the clinical uses of glutamine in AAD management.
keywords: Antibiotic-associated diarrhea glutamine intestinal barrier
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谷氨酰胺改善抗生素相关性腹泻的作用研究
摘要:腹泻反应是使用抗生素后的主要副作用,目前还没有已知的治疗方案。谷氨酰胺在肠道内环境稳定中起着关键作用,但其在抗生素相关性腹泻(AAD)中的作用尚不清楚。我们利用小鼠模型研究了补充谷氨酰胺在AAD中的作用。研究表明,灌胃克林霉素的小鼠结肠黏膜中的谷氨酰胺含量显著减少,而补充了谷氨酰胺后改善了实验性AAD的几种症状。进一步的研究机制表明,灌胃克林霉素后肠道微生物群发生紊乱,尤其是产丁酸盐菌株,从而导致粪便丁酸盐缺乏,进而增加了机体对谷氨酰胺的需求。谷氨酰胺对AAD的改善作用可以部分地通过恢复肠粘膜屏障和促进抗微生物宿主防御来解释。总之,我们在本研究中的发现为指导谷氨酰胺在AAD治疗中的临床应用提供了一个有价值的理论依据。
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