Glycolate is a Novel Marker of Vitamin B2 Deficiency Involved in Gut Microbe Metabolism in Mice

Abstract

Microbes in the human gut play a role in the production of bioactive compounds, including some vitamins. Although several studies attempted to identify definitive markers for certain vitamin deficiencies, the role of gut microbiota in these deficiencies is unclear. To investigate the role of gut microbiota in deficiencies of four vitamins, B2, B6, folate, and B12, we conducted a comprehensive analysis of metabolites in mice treated and untreated with antibiotics. We identified glycolate (GA) as a novel marker of vitamin B2 (VB2) deficiency, and show that gut microbiota sense dietary VB2 deficiency and accumulate GA in response. The plasma GA concentration responded to reduced VB2 supply from both the gut microbiota and the diet. These results suggest that GA is a novel marker that can be used to assess whether or not the net supply of VB2 from dietary sources and gut microbiota is sufficient. We also found that gut microbiota can provide short-term compensation for host VB2 deficiency when dietary VB2 is withheld.

Functional Roles of B‐Vitamins in the Gut and Gut Microbiome

“…The gut microbiota was able to provide compensatory riboflavin in the short-term when a dietary riboflavin deficiency was induced in mice ( Figure 2, Table 1). [43] The survival of axenic-but not conventional-Drosophila was significantly depressed when their diet lacked riboflavin. [44] Qi B et al showed the importance of live bacteria being able to provide micronutrients in the gut, such as riboflavin, to C. elegans (Table 1).…”

Effect of Vitamin B2‐Deficient Diet on Hydroxyproline‐ or Obesity‐Induced Hyperoxaluria in Mice

“…[ 33–35 ] We previously showed that administration of a vitamin B2 (VB2)‐deficient diet could decrease GO activity in the liver and lessen increases in plasma glycolate concentrations. [ 36 ] We also observed a negative correlation between GO activity in the liver and plasma glycolate concentrations, suggesting that VB2 deficiency in the liver inhibits metabolism of glycolate to glyoxylate due to reduced GO activity. [ 36 ] To explore this possibility, in the present study we investigated whether hyperoxaluria could be suppressed by feeding a VB2‐deficient diet to mice with hydroxyproline‐ or obesity‐induced hyperoxaluria.…”

“…[ 36 ] We also observed a negative correlation between GO activity in the liver and plasma glycolate concentrations, suggesting that VB2 deficiency in the liver inhibits metabolism of glycolate to glyoxylate due to reduced GO activity. [ 36 ] To explore this possibility, in the present study we investigated whether hyperoxaluria could be suppressed by feeding a VB2‐deficient diet to mice with hydroxyproline‐ or obesity‐induced hyperoxaluria. A better understanding of how a VB2‐deficient diet can affect hyperoxaluria will facilitate development of more effective therapies.…”

“…Hepatic glycolate oxidase (GO) activity was measured as reported. [ 36 ] Briefly, hepatic proteins were extracted in 10 volumes of assay buffer (My Bioscience M1358243218). Protein sample solutions were homogenized, sonicated, and centrifuged for 15 min at 12000× g and 4 °C.…”

“…All samples were prepared according to methods described by Human Metabolome Technologies, Inc. and in previous reports. [ 36,37 ] Briefly, the plasma and kidney were immediately frozen in liquid nitrogen and stored at ‐80 °C until extraction of metabolites. Samples were weighed and completely homogenized in ice‐cold methanol containing internal standards.…”