Plasma metabolomics changes comparing daytime to overnight infusions of home parenteral nutrition in adult patients with short bowel syndrome: secondary analysis of a clinical trial

Background Home parenteral nutrition (HPN) is often cycled nocturnally and is expected to result in glucose intolerance and sleep disruption partly due to circadian misalignment. This study aimed to define the metabolic response when HPN is cycled during the daytime compared to overnight. Methods This analysis leveraged samples from a clinical trial in adults with short bowel syndrome consuming HPN (ClinicalTrials.gov: NCT04743960). Enrolled patients received 1 week of HPN overnight followed by 1 week of HPN during the daytime. Fasting blood samples were collected following each study period and global metabolic profiles were determined from plasma. Differential metabolite abundance was determined from normalized and scaled data using adjusted Linear Models for MicroArray Data models followed by pathway enrichment analysis. Results Nine patients (mean age, 52.6years; 78%female; mean BMI 20.7kg/m2) provided samples. Among 622 identified metabolites, changes were observed in 36 metabolites at Punadj<0.05 with higher abundance of fatty acids, long-chain and polyunsaturated fatty acids (Dihomo-gamma-linolenic acid, arachidonate (20:4n6), docosahexaenoate (DHA;22:6n3)) and glycerolipids with daytime infusions. Enrichment analysis identified pathways related to the biosynthesis of unsaturated fatty acids, D-arginine, and D-ornithine metabolism, and linoleic acid metabolism (Punadj<0.05). Conclusion Daytime infusions of HPN may result in changes in circulating lipids and amino acid composing metabolic pathways previously implicated in circadian rhythms. As this is the first untargeted metabolomics study of HPN, larger studies are needed.