摘要
肠道菌群失衡与多种宿主疾病密切相关,靶向肠道菌群中的代谢通路也成为当前防治宿主疾病的前沿策略和研究热点。炎症性肠病(inflammatory bowel disease,IBD)是一组病因不明的慢性进展性肠道炎症疾病。已有研究证实IBD的发生和发展与肠道菌群紊乱以及细菌的呼吸能量代谢之间存在一定联系,本文将结合最新的研究进展,对三者之间的关系进行整理分析,并提出调控肠道菌群呼吸与能量代谢,缓解宿主肠道炎症新的治疗策略。在IBD发生发展时,肠道菌群稳态失衡,其原因主要包括两方面:①宿主肠道炎症发生时,肠腔内氧气含量增加,致使兼性厌氧菌尤其是肠杆菌科细菌异常增殖,而绝对厌氧菌如厚壁菌门等细菌的生长则受到抑制;②肠道炎症副产物也会支持兼性厌氧菌的扩增,最终加剧肠道菌群失衡。失调的肠道菌群会进一步加剧肠道免疫稳态失衡,加重肠道炎症反应。最新研究证实可通过干扰细菌呼吸及能量代谢,抑制促炎细菌的异常增殖进而恢复菌群稳态,减轻IBD炎症反应。通过以上分析,提示可聚焦肠道菌群中的代谢通路,调控肠道细菌呼吸以及能量代谢,探索缓解宿主肠道炎症的治疗策略,对于IBD的临床治疗以及创新药物研究具有重要意义。
Gut microbiota dysbiosis is closely related to a variety of host diseases.Recently,targeting the metabolic pathways of gut microbiota for the prevention and treatment of host diseases has become a frontier strategy and research hotspot.Inflammatory bowel disease(IBD)is a group of chronic progressive intestinal inflammatory diseases of unknown etiology.The relationship between IBD and gut microbiota disorders and bacterial respiratory/energy metabolism has been confirmed in recent research.This article will introduce the relationship among them,and propose a new treatment strategy to alleviate host gut inflammation by regulating gut microbiota respiration and energy metabolism based on the latest research progress.In the progression of IBD,the gut microbiota homeostasis is disturbed.The main reasons include two aspects:on the one hand,when the intestinal inflammation of the host occurs,with increasing of oxygen concentration in the intestinal cavity,facultative anaerobic bacteria,especially Enterobacteriaceae bacteria would proliferate abnormally;while the growth of absolute anaerobic bacteria such as Firmicutes is inhibited.On the other hand,intestinal inflammation by-products also support the expansion of facultative anaerobic bacteria,which ultimately exacerbates the imbalance of gut microbiota.Dysregulated intestinal flora will further disturb intestinal immune homeostasis and exacerbate intestinal inflammation.The latest research proposed the possibility that IBD can be alleviated by interfering with the respiration of bacteria,inhibiting the abnormal proliferation of bacteria,or increasing the level of"beneficial"metabolites of gut microbiota.The above studies suggest that alleviating host intestinal inflammation can be explored by focusing on the metabolic pathways of gut microbiota and regulating the intestinal bacterial respiration and energy metabolism,which is of great significance for the clinical treatment of IBD and the research of innovative drugs.
作者
李成曦
王颖异
李建萍
王雨萌
张森
段金廒
郭建明
LI Cheng-xi;WANG Ying-yi;LI Jian-ping;WANG Yu-meng;ZHANG Sen;DUAN Jin-ao;GUO Jian-ming(Jiangsu Key Laboratory of High Technology Research of TCM Formulae,Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources,Nanjing University of Chinese Medicine,Nanjing 210023,China)
出处
《药学学报》
CAS
CSCD
北大核心
2020年第9期2008-2018,共11页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81773983)。
关键词
炎症性肠病
肠道菌群
肠杆菌科
细菌呼吸
能量代谢
inflammatory bowel disease
gut bacteria
Enterobacteriaceae
bacterial respiration
energy metabolism
