The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD.

Zilu Cheng, Ling Yang, Huikuan Chu
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Abstract

Background: The liver disorders caused by alcohol abuse are termed alcoholic-related liver disease (ALD), including alcoholic steatosis, alcoholic steatohepatitis alcoholic hepatitis, and alcoholic cirrhosis, posing a significant threat to human health. Currently, ALD pathogenesis has not been completely clarified, which is likely to be related to the direct damage caused by alcohol and its metabolic products, oxidative stress, gut dysbiosis, and exosomes.

Aims: The existing studies suggest that both the gut microbiota and exosomes contribute to the development of ALD. Moreover, there exists an interaction between the gut microbiota and exosomes. We discuss whether this interaction plays a role in the pathogenesis of ALD and whether it can be a potential therapeutic target for ALD treatment.

Key scientific concepts of review: Chronic alcohol intake alters the diversity and composition of gut microbiota, which greatly contributes to ALD's progression. Some approaches targeting the gut microbiota, including probiotics, fecal microbiota transplantation, and phage therapy, have been confirmed to effectively ameliorate ALD in many animal experiments and/or several clinical trials. In ALD, the levels of exosomes and the expression profile of microRNA have also changed, which affects the pathogenesis of ALD. Moreover, there is an interplay between exosomes and the gut microbiota, which also putatively acts as a pathogenic factor of ALD.

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肠道微生物群、外泌体及其相互作用在 ALD 发病机制中的作用。
背景:酗酒导致的肝脏疾病被称为酒精相关性肝病(ALD),包括酒精性脂肪变性、酒精性脂肪性肝炎、酒精性肝炎和酒精性肝硬化,对人类健康构成重大威胁。目前,ALD 的发病机制尚未完全明确,可能与酒精及其代谢产物、氧化应激、肠道菌群失调和外泌体造成的直接损伤有关。此外,肠道微生物群和外泌体之间存在相互作用。我们将讨论这种相互作用是否在 ALD 的发病机制中发挥作用,以及它是否可以成为治疗 ALD 的潜在治疗靶点:慢性酒精摄入改变了肠道微生物群的多样性和组成,这在很大程度上导致了 ALD 的进展。一些针对肠道微生物群的方法,包括益生菌、粪便微生物群移植和噬菌体疗法,已在许多动物实验和/或一些临床试验中被证实能有效改善ALD。在 ALD 中,外泌体的水平和 microRNA 的表达谱也发生了变化,从而影响了 ALD 的发病机制。此外,外泌体与肠道微生物群之间存在相互作用,而肠道微生物群也可能是 ALD 的致病因素。
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