INSERM UMR1063, Stress Oxydant et Pathologies Métaboliques, Faculté de Santé, Université d'Angers, Université Bretagne Loire, Angers, France.
EA 3859, Hémodynamique, Interaction Fibrose et Invasivité Tumorales Hépatiques (HIFIH), Angers, France.
Am J Physiol Gastrointest Liver Physiol. 2021 Apr 1;320(4):G485-G495. doi: 10.1152/ajpgi.00362.2020. Epub 2021 Jan 20.
The liver and intestine communicate in a bidirectional way through the biliary tract, portal vein, and other components of the gut-liver axis. The gut microbiota is one of the major contributors to the production of several proteins and bile acids. Imbalance in the gut bacterial community, called dysbiosis, participates in the development and progression of several chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD). NAFLD is currently considered the main chronic liver disease worldwide. Dysbiosis contributes to NAFLD development and progression, notably by a greater translocation of pathogen-associated molecular patterns (PAMPs) in the blood. Lipopolysaccharide (LPS) is a PAMP that activates Toll-like receptor 4 (TLR4), induces liver inflammation, and participates in the development of fibrogenesis. LPS can be transported by bacterial extracellular vesicles (EVs). EVs are spherical structures produced by eukaryotic and prokaryotic cells that transfer information to distant cells and may represent new players in NAFLD development and progression. The present review summarizes the role of eukaryotic EVs, either circulating or tissue-derived, in NAFLD features, such as liver inflammation, angiogenesis, and fibrosis. Circulating EV levels are dynamic and correlate with disease stage and severity. However, scarce information is available concerning the involvement of bacterial EVs in liver disease. The present review highlights a potential role of bacterial EVs in insulin resistance and liver inflammation, although the mechanism involved has not been elucidated. In addition, because of their distinct signatures, eukaryotic and prokaryotic EVs may also represent a promising NAFLD diagnostic tool as a "liquid biopsy" in the future.
肝脏和肠道通过胆道、门静脉和其他肠道-肝脏轴的组成部分进行双向交流。肠道微生物群是产生几种蛋白质和胆汁酸的主要因素之一。肠道细菌群落的失衡，称为菌群失调，参与了几种慢性肝病的发生和发展，如非酒精性脂肪性肝病（NAFLD）。NAFLD 目前被认为是全球主要的慢性肝病。菌群失调参与了 NAFLD 的发生和发展，特别是通过血液中病原体相关分子模式（PAMPs）的更大易位。脂多糖（LPS）是一种 PAMP，它可以激活 Toll 样受体 4（TLR4），诱导肝脏炎症，并参与纤维化的发生。LPS 可以通过细菌细胞外囊泡（EVs）运输。EVs 是真核细胞和原核细胞产生的球形结构，将信息传递到远处的细胞，并且可能是 NAFLD 发展和进展的新参与者。本综述总结了真核 EVs（无论是循环的还是组织衍生的）在 NAFLD 特征中的作用，如肝脏炎症、血管生成和纤维化。循环 EV 水平是动态的，与疾病阶段和严重程度相关。然而，关于细菌 EVs 参与肝脏疾病的信息很少。本综述强调了细菌 EVs 在胰岛素抵抗和肝脏炎症中的潜在作用，尽管涉及的机制尚未阐明。此外，由于其独特的特征，真核和原核 EVs 也可能成为未来 NAFLD 的一种有前途的诊断工具，作为一种“液体活检”。
