Abstract
Objectives
Metabolomic profiling of plasma provides a biochemical fingerprint of the circulating metabolites from the host and microbiome, and may assist with understanding mechanisms underlying functional gastrointestinal (GI) disorders such as Irritable Bowel Syndrome (IBS). In a case-control study, we aimed to identify microbial and host factors in plasma to provide mechanistic insights into functional GI disorders and increase the predictability of phenotypes for use in nutrition intervention studies.
Methods
Plasma samples from 246 individuals with functional GI disorders (cases) or asymptomatic (controls), consisting of 93 healthy controls, 54 with functional constipation (C) or IBS-C, 60 with functional diarrhoea (D) or IBS-D, and 39 diagnosed as IBS-mixed or awaiting diagnosis. Plasma was subjected to biphasic extraction and global metabolite profiling was performed using three separate untargeted liquid chromatography high resolution mass spectrometry analysis (LC-MS) methods (polar, semi-polar and non-polar chromatography).
Results
Plasma metabolomic profiles differed considerably between the IBS phenotypes and those of the control subjects. Multivariate partial least squares discriminant analysis of 428 annotated lipid species highlighted significant differences (P < 0.001) between IBS-C and healthy control subjects. Univariate analysis revealed significant differences in the concentrations of 48 lipid species (P < 0.05) between the two groups, including elevated concentrations of many sphingolipids and phospholipids in the IBS-C group. Biochemical network analysis also revealed major perturbations in amino acid, bile acid and lipid metabolism, and highlighted key metabolic pathways included microbial related pathways.
Conclusions
Perturbations of plasma lipid concentrations in the IBS subjects suggest changes may occur with both host and microbial lipid metabolism. Future efforts to investigate these links will utilize a systems biology approach integrating metabolomic and fecal metagenomic datasets to further identify key pathways and biomarkers that characterize functional GI disorders and how nutrition can improve GI health and function.
Funding Sources
Funded by the New Zealand National Science Challenge High-Value Nutrition program.