Shared molecular features and potential diagnostic biomarkers between ulcerative colitis and sarcopenia: an integrative bioinformatics analysis with preliminary experimental validation

Sarcopenia and ulcerative colitis (UC) may share potential biological links through mechanisms involving immune dysregulation, gut microbiota imbalance, and inflammatory pathway activation. This study aimed to identify fatty acid metabolism-related shared genes between UC and sarcopenia. A total of 277 shared differentially expressed genes (sDEGs) were identified, which were mainly enriched in immune-, inflammation-, and metabolism-related pathways. By intersecting the sDEGs with fatty acid metabolism-related gene sets, 13 fatty acid metabolism-related shared differentially expressed genes (FAM-sDEGs) were obtained, and unsupervised clustering based on these genes stratified UC patients into distinct molecular subtypes. Using machine learning and feature-ranking methods, PHYH and HSD17B3 were ultimately identified as key hub genes. ROC analysis showed that these two genes exhibited diagnostic value for both sarcopenia and UC across multiple datasets. In addition, the expression of the hub genes was significantly associated with immune cell infiltration profiles and was further validated in independent datasets. Preliminary validation in a UC cell model confirmed the downregulation of PHYH, while immunohistochemical analysis of colonic tissues further supported the downregulated expression of PHYH in patients with UC, consistent with the bioinformatics results. Collectively, these findings suggest that fatty acid metabolism may play an important role in the shared molecular features between UC and sarcopenia, and that PHYH may serve as potential diagnostic biomarkers.