Metabolomics Reveals Altered Hepatic Bile Acids, Gut Microbiome Metabolites, and Cell Membrane Lipids Associated with Marginal Vitamin A Deficiency in a Mongolian Gerbil Model.

Abstract

This study is designed to provide a broad evaluation of the impacts of vitamin A (VA) deficiency on hepatic metabolism in a gerbil model. After 28 days of VA depletion, male Mongolian gerbils (Meriones unguiculatus) are randomly assigned to experimental diets for 28 days. Groups are fed a white-maize-based diet with ≈50µL cottonseed oil vehicle either alone (VA-, n=10) or containing 40µg retinyl acetate (VA+, n=10) for 28 days. Liver retinol is measured by high-performance liquid chromatography. Primary metabolomics, aminomics, lipidomics, bile acids, oxylipins, ceramides, and endocannabinoids are analyzed in post-mortem liver samples by liquid chromatography-mass spectrometry. Liver retinol is lower (p<0.001) in the VA- versus VA+ group, with concentrations indicating marginal VA deficiency. A total of 300 metabolites are identified. Marginal VA deficiency is associated with lower bile acids, trimethylamine N-oxide, and a variety of acylcarnitines, phospholipids and sphingomyelins (p<0.05). Components of DNA, including deoxyguanosine, cytidine, and N-carbomoyl-beta-alanine (p<0.05), are differentially altered. Hepatic metabolomics in a marginally VA-deficient gerbil model revealed alterations in markers of the gut microbiome, fatty acid and nucleotide metabolism, and cellular structure and signaling.