Fecal microbiota transplantation from Helicobacter pylori carriers following bismuth quadruple therapy exacerbates alcohol-related liver disease in mice via LPS-induced activation of hepatic TLR4/NF-κB/NLRP3 signaling

作者：Huihui Gao, Hangming Bai, Su Y, Yuting Gao, Hui Fang, Donghang Li, Youren Yu, Lu Xing, Dasheng Xia, Daqing Mao, Yi Luo · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06573-5 · 被引用次数：11 · 研究领域：Alcohol Consumption and Health Effects、Helicobacter pylori-related gastroenterology studies、Gut microbiota and health

BACKGROUND: Helicobacter pylori infection is common in patients with alcohol-related liver disease (ALD), and bismuth quadruple therapy (BQT) is widely used for eradication. However, its impact on ALD remains unclear. This study aims to characterize BQT-induced gut microbiota alterations in asymptomatic H. pylori carriers and evaluate their effect on an ALD mouse model. METHODS: Metagenomic sequencing was conducted to assess the gut microbiota composition of individuals before and after BQT. Fecal microbiota transplantation (FMT) from these donors was performed in an ALD mouse model. Gut microbiota in mice was analyzed by 16S rRNA sequencing. Liver and intestinal parameters were assessed using western blot, RT-qPCR, histopathology, ELISA, and flow cytometry. RESULTS: BQT treatment significantly altered the gut microbiota in H. pylori carriers, increasing the abundance of opportunistic pathogens, including Klebsiella pneumoniae, Escherichia coli, Klebsiella quasipneumoniae, and Klebsiella variicola, while decreasing beneficial bacteria such as Bifidobacterium, Eubacterium, Bacteroides, Faecalibacterium, and Blautia. In ALD mice receiving FMT from post-BQT donors, exacerbated gut dysbiosis was observed, marked by an enrichment of Enterobacteriaceae and Escherichia-Shigella. These microbiota changes were associated with impairment of intestinal barrier integrity, as evidenced by reduced levels of mucins, tight junction proteins, and antimicrobial peptides, along with a decrease ...