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自噬与炎症性肠病(IBD)发病机制中的代谢性宿主-微生物群相互作用

Metabolic Host-Microbiota Interactions in Autophagy and the Pathogenesis of Inflammatory Bowel Disease (IBD).

作者信息

Dowdell Alexander S, Colgan Sean P

机构信息

Department of Medicine and the Mucosal Inflammation Program, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA.

出版信息

Pharmaceuticals (Basel). 2021 Jul 22;14(8):708. doi: 10.3390/ph14080708.

Abstract

Inflammatory bowel disease (IBD) is a family of conditions characterized by chronic, relapsing inflammation of the gastrointestinal tract. IBD afflicts over 3 million adults in the United States and shows increasing prevalence in the Westernized world. Current IBD treatments center on modulation of the damaging inflammatory response and carry risks such as immunosuppression, while the development of more effective treatments is hampered by our poor understanding of the molecular mechanisms of IBD pathogenesis. Previous genome-wide association studies (GWAS) have demonstrated that gene variants linked to the cellular response to microorganisms are most strongly associated with an increased risk of IBD. These studies are supported by mechanistic work demonstrating that IBD-associated polymorphisms compromise the intestine's anti-microbial defense. In this review, we summarize the current knowledge regarding IBD as a disease of defects in host-microbe interactions and discuss potential avenues for targeting this mechanism for future therapeutic development.

摘要

炎症性肠病(IBD)是一类以胃肠道慢性复发性炎症为特征的疾病。在美国,超过300万成年人患有IBD,并且在西方化世界中其患病率呈上升趋势。目前IBD的治疗主要集中在调节有害的炎症反应上,存在免疫抑制等风险,而由于我们对IBD发病机制的分子机制了解不足,更有效治疗方法的开发受到阻碍。先前的全基因组关联研究(GWAS)表明,与细胞对微生物的反应相关的基因变异与IBD风险增加的关联最为密切。这些研究得到了机制研究的支持,表明IBD相关的多态性损害了肠道的抗菌防御。在这篇综述中,我们总结了目前关于IBD作为宿主-微生物相互作用缺陷疾病的知识,并讨论了针对这一机制进行未来治疗开发的潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2981/8399382/60fcbc29eb91/pharmaceuticals-14-00708-g001.jpg

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