Vitamin A deficiency in mice alters host and gut microbial metabolism leading to altered energy homeostasis

Vitamin A deficiency (A) is a worldwide public health problem. To better understand how vitamin A status influences gut microbiota and host metabolism, we systematically analyzed urine, cecum, serum and liver samples from vitamin A sufficient (A+) and deficient (A) mice using H-1 NMR-based metabolomics, quantitative (q)PCR and 16S rRNA gene sequencing coupled with multivariate data analysis. The microbiota in the cecum of A mice showed compositional as well as functional shifts compared to the microbiota from A+ mice. Targeted 1H NMR analyses revealed significant changes in microbial metabolite concentrations including higher butyrate and hippurate and decreased acetate and 4-hydroxyphenylacetate in A+ relative to A mice. Bacterial butyrate producing genes including butyryl-CoA:acetate CoA-transferase and butyrate kinase were significantly higher in bacteria from A+ versus bacteria from A mice. A mice had disturbances in multiple metabolic pathways including alterations in energy (hyperglycemia, glycogenesis, TCA cycle and lipoprotein biosynthesis), amino acid and nucleic acid metabolism. A mice had hyperglycemia, liver dysfunction, changes in bacterial metabolism and altered gut microbial communities. Moreover, integrative analyses indicated a strong correlation between gut microbiota and host energy metabolism pathways in the liver. Vitamin A regulates host and bacterial metabolism, and the result includes alterations in energy homeostasis. (C) 2017 Elsevier Inc. All rights reserved.