Vitamin A deficiency in mice alters host and gut microbial metabolism leading to altered energy homeostasis
2017
Tian, Yuan | Nichols, Robert G. | Cai, Jingwei | Patterson, Andrew D. | Cantorna, Margherita T.
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 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 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.
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