数字农科院2.0

Bile acid synthesis dysregulation in liver diseases promotes ectopic expansion of oral streptococci in the intestine

文献类型： 外文期刊

作者： Yugui Wang;Wenjie Mu;Jian Guan;Pingping Ma;Yaqi Li;Ying Zhang;Wenjun Zhu;Yu Zhou;Yang Zou;Tongxu Zeng;Jian Zhou;Xiaoqi Lin;Xuehua Yan;Wenjuan Shi;Xiaola Guo;Xing Quan Zhu;Xuepeng Cai;Yan Sun;Aijiang Guo;Shuai Wang

作者机构：

关键词： bile acid;CP: Microbiology;gut microbiome;liver disease;liver echinococcosis;oral microbes

期刊名称： Cell Reports

ISSN： 2211-1247

年卷期： 2025 年 44 卷 10 期

页码：

收录情况： SCIE（2025版）

摘要： Liver diseases often coincide with dysregulated gut homeostasis and Streptococcus overgrowth, yet the underlying mechanisms remain unclear. Here, we study patients with liver echinococcosis and other liver conditions. We observe that these patients frequently exhibit a co-occurrence of an ectopic expansion of orally derived Streptococcus species implicated in intestinal inflammation, alongside a bile acid deficiency in the gut. This association is typically characterized by the reduction of 12-ketolithocholic acid (12-KetoLCA), which exerts potent membrane-disrupting activity. We show that liver disorders compromise gut resistance to oral microbes due to a loss of ecological control from bile acids, particularly 12-KetoLCA. This bile-acid-conferred gut barrier is regulated by cytochrome P450 enzymes and can be reconstituted through adeno-associated virus (AAV) gene therapy targeting these genes. Additionally, we reveal that supplementation with 12-KetoLCA prevents oral Streptococcus-driven gut inflammation through antibacterial activity. Our findings underscore the essential role of bile acids in maintaining the oral-gut barrier.

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