Low Plasma Choline in Cystic Fibrosis Patients Is Linked to Exocrine Pancreatic Insufficiency and Small Intestinal Bacterial Overgrowth

Background: Exocrine pancreatic insufficiency in Cystic Fibrosis (CF) increases fecal choline losses, but the postnatal course of plasma choline and its metabolites in these patients is un-known. While choline homeostasis is crucial for cellular, bile, and lipoprotein metabolism, via phosphatidylcholine (PC) and via betaine as a methyl donor, choline deficiency is associated with impaired lung and liver function, including hepatic steatosis. Objective: To assess plasma levels of choline, betaine, trimethylamine oxide (TMAO), PC, and PC subclasses in CF patients from infancy to adulthood, comparing those with exocrine pancreatic insufficiency (EPI) and sufficiency (EPS). Methods: Retrospective analysis of target parameters in plasma samples (7/2015-11/2023) of CF patients (0.64-24.6 years) with tandem mass spectrometry. Results: A total of 477 samples from 162 CF patients were analyzed. In CF patients with EPI (N=148), plasma choline and betaine concentrations were lower, and decreased with age compared to EPS pa-tients showing normal values. TMAO concentrations, indicating intestinal choline degradation by bacterial colonization, were frequently elevated in EPI from infancy onwards, and inversely related to plasma choline and betaine levels. PC-containing linoleic acid levels were lower in EPI, but arachidonic and docosahexaenoic acid content was similar in both patient groups. Con-clusion: CF patients with EPI are at risk of choline and betaine deficiency compared to exocrine pancreas-sufficient CF patients. Elevated TMAO concentrations in EPI patients indicate in-creased bacterial colonization leading to choline degradation before absorption. These findings indicate that laboratory testing of choline, betaine and TMAO, and clinical trials on choline supplementation are warranted in CF patients.