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肠道疾病发病机制和治疗中微生物群-线粒体串扰的作用。

The role of microbiota-mitochondria crosstalk in pathogenesis and therapy of intestinal diseases.

机构信息

Department of Gastroenterology, Peking University Third Hospital, No.49 North Garden Road, Haidian District, Beijing 100191, China.

Department of Gastroenterology, Peking University Third Hospital, No.49 North Garden Road, Haidian District, Beijing 100191, China.

出版信息

Pharmacol Res. 2022 Dec;186:106530. doi: 10.1016/j.phrs.2022.106530. Epub 2022 Oct 29.

Abstract

The interaction between mitochondria and gut microbiota plays a critical role in intestinal physiological homeostasis. In this kind of homeostasis, intestinal epithelial hypoxia helps microbiota to be dominated by obligate anaerobes, who provide their benefit metabolites for the host, such as short chain fatty acids (SCFAs). In addition, emerging studies suggest that microbial signals to the mitochondria of intestinal epithelial cells (IECs) could alter mitochondrial ultrastructure and its metabolic function, induce inflammasome activation and disrupt epithelial hypoxia. Conditions that alter the mitochondria could lead to intestinal epithelium inflammation and oxygenation, both of which would drive an expansion of facultative anaerobes and exacerbate the imbalance of mitochondria-microbiota crosstalk. This phenomenon has proved to be associated with the pathogenesis of gastrointestinal (GI) diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Therefore, in this review, we summarized the recent process on the interaction between mitochondria of IECs and gut microbiota in the case of both GI physiological homeostasis and diseases, and potential therapeutic interventions targeting mitochondria-microbiota crosstalk in GI diseases.

摘要

线粒体与肠道微生物群的相互作用在肠道生理稳态中起着关键作用。在这种稳态中,肠道上皮缺氧有助于微生物群被专性厌氧菌所主导,后者为宿主提供有益的代谢物,如短链脂肪酸 (SCFAs)。此外,新兴的研究表明,微生物信号可以改变肠道上皮细胞 (IECs) 的线粒体超微结构及其代谢功能,诱导炎症小体的激活并破坏上皮缺氧。改变线粒体的条件会导致肠道上皮炎症和缺氧,这两者都会导致兼性厌氧菌的扩张,并加剧线粒体-微生物群相互作用的失衡。这种现象已被证明与胃肠道 (GI) 疾病的发病机制有关,包括炎症性肠病 (IBD) 和结直肠癌 (CRC)。因此,在这篇综述中,我们总结了 IECs 的线粒体与肠道微生物群在 GI 生理稳态和疾病中的相互作用的最新进展,以及针对 GI 疾病中线粒体-微生物群相互作用的潜在治疗干预措施。

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