ArticleScientific reports2026
Targeted metabolomics reveals serum biomarkers and metabolic alterations in cholesterol gallstone patients.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The molecular mechanisms underlying cholesterol gallstone (CG) formation remain incompletely elucidated, and effective diagnostic biomarkers are lacking. This study integrates high-resolution ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) with high-throughput targeted metabolomics to systematically reveal the serum metabolic profile of CG patients. The goal is to elucidate the pathological mechanisms of CG and identify potential high-value biomarkers. Serum samples were collected from 39 CG patients (who underwent laparoscopic cholecystectomy) and 32 healthy controls at Fudan University Affiliated Pudong Hospital between January 1, 2023, and March 1, 2024. A UHPLC-MS platform was utilized to precisely quantify 354 metabolites. Multivariate statistical analyses, pathway enrichment analysis, and receiver operating characteristic (ROC) curve evaluations were performed to assess the diagnostic efficacy of differentially expressed metabolites. A total of 100 significantly altered metabolites were identified, with notable enrichment in amino acid metabolism, including alanine, threonine, and deoxycholic acid (P < 0.01). The activity of ATP-binding cassette (ABC) transporter pathways was significantly downregulated (P < 0.001), suggesting a strong association between cholesterol homeostasis imbalance and gallstone formation. Notably, nucleotide metabolites such as S-adenosylmethionine exhibited high diagnostic potential, with an area under the ROC curve (AUC) ranging from 0.913 to 0.984. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis further highlighted amino acid metabolism, nucleotide metabolism, and carbon metabolism as central hubs of metabolic reprogramming in CG. This study systematically employed high-resolution UHPLC-MS-based targeted metabolomics to delineate the serum metabolic characteristics of CG. The findings reveal that dysregulation of amino acid and nucleotide metabolism is a key driver of disease progression. The identified metabolic biomarkers hold promise for assisting in CG diagnosis, while the discovery of ABC transporter and mucin synthesis-related pathways opens new avenues for targeted therapy. These results not only enhance the understanding of the molecular mechanisms of cholelithiasis but also provide a theoretical and technical foundation for precision medicine strategies.
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