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

Scope This study was designed to provide a broad evaluation of the impacts of vitamin A (VA) deficiency on hepatic metabolism in a gerbil model. Methods and results After 28d of VA depletion, male Mongolian gerbils (Meriones unguiculatus) were randomly assigned to experimental diets for 28 d. Groups were fed a white maize‐based diet with ∼50 μL cottonseed oil vehicle either alone (VA−, n = 10) or containing 40 μg retinyl acetate (VA+, n = 10) for 28 d. Liver retinol was measured by high‐performance liquid chromatography (HPLC). Primary metabolomics, aminomics, lipidomics, bile acids, oxylipins, ceramides and endocannabinoids were determined in post‐mortem liver samples by liquid chromatography‐mass spectrometry (LC‐MS). Results Liver retinol was lower (p < 0.001) in the VA− versus VA+ group, with concentrations indicating marginal VA deficiency. A total of 300 metabolites were identified. Marginal VA deficiency was associated with lower bile acids, trimethylamine N‐oxide, and a variety of acyl carnitines, phospholipids and sphingomyelins (p < 0.05). Components of DNA, including purine deoxyribonucleosides, deoxyguanosine, the nucleoside cytidine, and the uracil derivative N‐carbomoyl‐beta‐alanine (p < 0.05), were differentially altered. Conclusions 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. This article is protected by copyright. All rights reserved