Choline and Choline-Related Metabolites in Pediatric Short Bowel Syndrome

Background: Choline is an essential nutrient crucial for liver function. It is required for bile and lipoprotein secretion and the synthesis of both phosphatidylcholine (PC) to ensure tissue homeostasis and betaine as a methyl donor. Choline deficiency has been implicated in the pathogenesis of intestinal failure-associated liver disease (IFALD), with the strongest evidence for its contribution to hepatic steatosis in patients with short bowel syndrome (SBS). Contributing factors are (1) an impaired recycling of choline from bile PC, leading to fecal choline losses; (2) small bowel bacterial overgrowth resulting in choline degradation prior to absorption; and (3) parenteral nutrition (PN) insufficient to meet choline requirements. However, data on choline status and its metabolites in pediatric patients with SBS are scarce. Objective: To investigate plasma levels of choline and choline-related metabolites in children with SBS and evaluate differences according to PN dependency and the presence of hepatic steatosis. Methods: Retrospective analysis of data from SBS patients managed at our intestinal rehabilitation program between March 2021 and July 2025. Target parameters in plasma samples were measured using tandem mass spectrometry. Statistical analysis and group comparison of laboratory and clinical data were performed. Results: A total of 127 samples from 80 children with SBS (0.2-17.9 years) were analyzed. Plasma choline, betaine, and PC concentrations were low, with 25% of patients showing markedly reduced choline and betaine levels below 6.4 µmol/L and 16 µmol/L, respectively. TMAO concentrations, indicating bacterial choline degradation, showed extreme variability (0-30 µmol; normal < 3 µmol/L), being inversely correlated with plasma choline levels. PC subgroups containing eicosapentaenoic acid and docosahexaenoic acid were increased in patients receiving PN. However, the only difference between steatotic and non-steatotic patients was the decreased plasma concentrations of both choline and betaine. Conclusions: Patients with SBS, with and without PN, are at risk of choline and betaine deficiency, which is associated with IFALD-steatosis. Controlled trials on choline supplementation in pediatric patients with SBS are warranted.