Murine vitamin A deficiency results in a hypermetabolic state and alterations in bacterial community structure and metabolism.

Vitamin A deficiency (A-) is a significant 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 vitamin A deficient (A-) mice using 1H 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 decreased butyrate and hippurate with increased 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 lower in bacteria from A- versus bacteria from A+ mice. A- mice had disturbances in multiple metabolic pathways including alterations in energy metabolism (hyperglycemia, glycogenesis, TCA cycle, and lipoprotein biosynthesis) and the A- host showed metabolites indicative of a hypermetabolic state (higher levels of amino acids and nucleic acids). 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 the microbiota, bacterial metabolism and the effects of vitamin A on the microbiota results in alterations in host metabolism.