Vanadyl sulfate supplementation alters the intestinal microbiome and bile acid metabolism

Abstract

Less than 10 μg/kg body weight (BW) vanadium (V) is consumed daily by humans in their diet and drinking water. V in the form of vanadyl sulfate (V⁺⁴) is promoted as an over-the-counter supplement with anti-diabetic effects and is consumed by some individuals at up to 200 μg/kg BW per day in dietary supplements. The impact of long-term consumption of high-dose V supplements on intestinal microbial communities and intestinal metabolomics is not known. This project tested the hypothesis that long-term intake of high-dose supplemental vanadyl sulfate alters the intestinal microbiome and metabolome in mice. In this study, four-week-old C57BL/6 J female mice were fed standard mouse food and provided V⁺⁴ (0.02, 0.2, 2 mg/L in drinking water) or control drinking water (0 μg V⁺⁴/d) for 6 months. Cecal contents were analyzed with 16S rRNA microbiome sequencing and liquid chromatography-high-resolution mass spectrometry. Biostatistics, bioinformatics, community detection, and metabolic pathway enrichment analysis were used to characterize vanadyl sulfate-dependent changes to the cecal microbiome and metabolome. Pathway analysis of metabolomics data identified alterations to bile acid metabolism, likely by altering reabsorption, and inflammatory pathways including arachidonic acid and linoleate metabolism. Bile acids including cholic acid, chenodeoxycholic acid/deoxycholic acid, and lithocholic acid were decreased in V⁺⁴-treated animals. In addition, altered arachidonic acid levels associated with inflammatory pathways were observed. Integrated microbiome-metabolome analysis identified unique communities with inflammation-related metabolites as well as metabolites and microbes linked to bile acid metabolism. In summary, chronic high-dose V⁺⁴ exposure at levels similar to human dietary supplement use altered bile acid metabolism and inflammatory pathways and resulted in compositional changes to the microbiome.