Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway.

IF 5.7 2区 生物学
Ruonan Zhang, Xuewei Sun, Han Lu, Xinrui Zhang, Mingyan Zhang, Xuewen Ji, Xinyi Yu, Chengliang Tang, Zihan Wu, Yinghua Mao, Jin Zhu, Minjun Ji, Zhan Yang
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Abstract

Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear. We utilised bacterial 16S rRNA gene profiling, antimicrobial treatments, and faecal microbiota transplantation tests to explore whether DSF therapy for ALI is dependent on gut microbiota. Our findings indicate that DSF primarily restores intestinal microbiome balance by modulating the abundance of Akkermansia muciniphila (A. muciniphila), leading to significant alleviation of ALI symptoms in a gut microbiota dependent manner. We also found that A. muciniphila can promote the activation of PI3K/Akt pathway, correct the Bcl-2/Bax ratio, and further inhibit hepatocyte apoptosis. In conclusion, DSF ameliorates ALI by modulating the intestinal microbiome and activating the PI3K/AKT pathway through A. muciniphila.

嗜粘杆菌通过PI3K/Akt通路介导双硫仑对急性肝损伤的预防作用
对乙酰氨基酚引起的急性肝损伤(ALI)发病率高,是一个严重的医学问题,但缺乏有效的治疗方法。肠肝轴因其在肝脏疾病中的重要作用而成为近年来关注的靶点之一。双硫仑(DSF)是一种多靶点药物,已被证明在多种肝脏疾病中发挥作用,并可影响肠道菌群,但是否能缓解ALI尚不清楚。我们利用细菌16S rRNA基因谱、抗菌治疗和粪便微生物群移植试验来探索ALI的DSF治疗是否依赖于肠道微生物群。我们的研究结果表明,DSF主要通过调节嗜muciniphila(嗜muciniphila)的丰度来恢复肠道微生物群平衡,从而以肠道微生物群依赖的方式显著缓解ALI症状。我们还发现嗜muciniphila可促进PI3K/Akt通路的激活,纠正Bcl-2/Bax比值,进而抑制肝细胞凋亡。综上所述,DSF通过调节肠道菌群和激活PI3K/AKT通路来改善ALI。
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来源期刊
Microbial Biotechnology
Microbial Biotechnology Immunology and Microbiology-Applied Microbiology and Biotechnology
CiteScore
11.20
自引率
3.50%
发文量
162
审稿时长
1 months
期刊介绍: Microbial Biotechnology publishes papers of original research reporting significant advances in any aspect of microbial applications, including, but not limited to biotechnologies related to: Green chemistry; Primary metabolites; Food, beverages and supplements; Secondary metabolites and natural products; Pharmaceuticals; Diagnostics; Agriculture; Bioenergy; Biomining, including oil recovery and processing; Bioremediation; Biopolymers, biomaterials; Bionanotechnology; Biosurfactants and bioemulsifiers; Compatible solutes and bioprotectants; Biosensors, monitoring systems, quantitative microbial risk assessment; Technology development; Protein engineering; Functional genomics; Metabolic engineering; Metabolic design; Systems analysis, modelling; Process engineering; Biologically-based analytical methods; Microbially-based strategies in public health; Microbially-based strategies to influence global processes
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