Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics

作者：Ye Liu, H X Li, Tieying Sun, Gaoyuan Sun, Boyue Jiang, Meilan Liu, Qing Wang, Tong Li, Jianfu Cao, Li Zhao, Fei Xiao, Fangqing Zhao, Hongyuan Cui · 发表于：iMeta · 年份：2025 · DOI：10.1002/imt2.70000 · 被引用次数：6 · 研究领域：Gallbladder and Bile Duct Disorders、Gut microbiota and health、Helicobacter pylori-related gastroenterology studies

Abstract Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross‐sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome‐targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3−V4 16S rRNA sequencing. Next, 60 samples (30 age‐ and sex‐matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography‐mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight‐week‐old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics‐treated mice. The effects of short‐chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet‐induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi‐omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine meta...