Sarcopenia in patients with active ulcerative colitis: associations with serum metabolites and gut microbiota.

BACKGROUND: Sarcopenia has garnered increasing attention in ulcerative colitis (UC) owing to its association with adverse clinical outcomes; however, its pathogenesis in the context of UC remains insufficiently characterized. METHODS: Hospitalized patients aged 18-70 years with active UC were consecutively enrolled at the Department of Gastroenterology, Peking Union Medical College Hospital, and age-matched healthy controls (HCs) were recruited. Body composition was assessed by bioelectrical impedance analysis (BIA), and muscle strength was evaluated by handgrip strength. Sarcopenia was diagnosed in accordance with the Asian Working Group for Sarcopenia (AWGS) 2025 consensus. Serum high-sensitivity C-reactive protein (hsCRP) of patients was recorded at admission. Intestinal barrier function was evaluated by serum diamine oxidase (DAO). Serum metabolites were profiled by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Gut microbiota composition and functional pathways were analyzed using metagenomic sequencing. RESULTS: Fifty-seven patients with active UC and 35 HCs were enrolled. The prevalence of sarcopenia, myopenia, and low muscle strength in the UC cohort was 40.4, 50.9, and 64.9%, respectively. Serum hsCRP was significantly higher in UC patients with sarcopenia (p = 0.011), whereas serum DAO showed no significant difference between UC patients with and without sarcopenia. Primary bile acids (BAs), conjugated BAs, and conjugated primary BAs were significantly increased, while hippuric acid, valerylcarnitine, and 2-methylbutyrylcarnitine were significantly decreased, in sarcopenic relative to non-sarcopenic UC patients (all p < 0.05). However, the association between serum hippuric acid and sarcopenia was not significant after adjusting for disease activity and hsCRP. At the genus level, Bacteroides and Streptococcus were the most prominently decreased and increased taxa in sarcopenic UC patients, respectively. Metagenomic functional analysis revealed that the relative abundance of the protein digestion and absorption pathway was significantly lower in sarcopenic UC patients (p = 0.030). CONCLUSION: UC-related sarcopenia exhibits notable associations with systemic inflammation, gut dysbiosis, and perturbations in circulating metabolites, including BAs and acylcarnitines.