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

ABSTRACT: 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.

SUBMITTER: Tian Y

PROVIDER: S-EPMC5866754 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Tian Yuan Y Nichols Robert G RG Cai Jingwei J Patterson Andrew D AD Cantorna Margherita T MT

The Journal of nutritional biochemistry 20171105

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 <sup>1</sup>H 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 comp ...[more]

PMID: 29227833

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Project description:Chronically elevated glucocorticoid levels impair cognition and are pro-inflammatory in the brain. Deficiency or inhibition of 11?-hydroxysteroid dehydrogenase type-1 (11?-HSD1), which converts inactive into active glucocorticoids, protects against glucocorticoid-associated chronic stress- or age-related cognitive impairment. Here, we hypothesised that 11?-HSD1 deficiency attenuates the brain cytokine response to inflammation. Because inflammation is associated with altered energy metabolism, we also examined the effects of 11?-HSD1 deficiency upon hippocampal energy metabolism. Inflammation was induced in 11?-HSD1 deficient (Hsd11b1Del/Del) and C57BL/6 control mice by intraperitoneal injection of lipopolysaccharide (LPS). LPS reduced circulating neutrophil and monocyte numbers and increased plasma corticosterone levels equally in C57BL/6 and Hsd11b1Del/Del mice, suggesting a similar peripheral inflammatory response. However, the induction of pro-inflammatory cytokine mRNAs in the hippocampus was attenuated in Hsd11b1Del/Del mice. Principal component analysis of mRNA expression revealed a distinct metabolic response to LPS in hippocampus of Hsd11b1Del/Del mice. Expression of Pfkfb3 and Ldha, key contributors to the Warburg effect, showed greater induction in Hsd11b1Del/Del mice. Consistent with increased glycolytic flux, levels of 3-phosphoglyceraldehyde and dihydroxyacetone phosphate were reduced in hippocampus of LPS injected Hsd11b1Del/Del mice. Expression of Sdha and Sdhb, encoding subunits of succinate dehydrogenase/complex II that determines mitochondrial reserve respiratory capacity, was induced specifically in hippocampus of LPS injected Hsd11b1Del/Del mice, together with increased levels of its product, fumarate. These data suggest 11?-HSD1 deficiency attenuates the hippocampal pro-inflammatory response to LPS, associated with increased capacity for aerobic glycolysis and mitochondrial ATP generation. This may provide better metabolic support and be neuroprotective during systemic inflammation or aging.

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

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

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