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微生物遗传毒素引发的与线粒体功能障碍相关的宿主 DNA 突变,是结直肠癌发生的一个重要因素。

Microbial genotoxin-elicited host DNA mutations related to mitochondrial dysfunction, a momentous contributor for colorectal carcinogenesis.

机构信息

Department of Infectious Disease and Hepatic Disease, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.

School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.

出版信息

mSystems. 2024 Sep 17;9(9):e0088724. doi: 10.1128/msystems.00887-24. Epub 2024 Aug 27.

Abstract

Gut microbe dysbiosis increases repetitive inflammatory responses, leading to an increase in the incidence of colorectal cancer. Recent studies have revealed that specific microbial species directly instigate mutations in the host nucleus DNA, thereby accelerating the progression of colorectal cancer. Given the well-established role of mitochondrial dysfunction in promoting colorectal cancer, it is reasonable to postulate that gut microbes may induce mitochondrial gene mutations, thereby inducing mitochondrial dysfunction. In this review, we focus on gut microbial genotoxins and their known and potential targets in mitochondrial genes. Consequently, we propose that targeted disruption of genotoxin transport pathways may effectively reduce the rate of mitochondrial gene mutations and yield substantial benefits for the prevention of colorectal carcinogenesis.

摘要

肠道微生物失调会增加重复性炎症反应,从而导致结直肠癌发病率上升。最近的研究表明,特定的微生物物种会直接引发宿主核 DNA 突变,从而加速结直肠癌的发展。鉴于线粒体功能障碍在促进结直肠癌中的作用已得到充分证实,因此可以合理地假设肠道微生物可能会诱导线粒体基因突变,从而导致线粒体功能障碍。在这篇综述中,我们重点关注肠道微生物遗传毒素及其在线粒体基因中的已知和潜在靶标。因此,我们提出靶向破坏遗传毒素转运途径可能会有效降低线粒体基因突变率,并为预防结直肠癌发生带来实质性的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ca/11406885/f5ef4d45874f/msystems.00887-24.f001.jpg

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