Abstract
Vitamin D is important in multiple health conditions. Vitamin D deficiency is prevalent globally even with exposure to adequate sunlight. Reduction in provitamin D3 (7-dehydrocholesterol, 7-DHC) is an important cause of vitamin D3 deficiency. Vitamin supplementation, food fortification, and use of probiotics are some approaches to reduce vitamin D3 deficiency. This study investigates plausibility of 7-DHC biosynthesis through dietary prebiotics supplementation. Furthermore, it reports mechanistic details and constraints for the biosynthesis using flux balance analysis (FBA) simulations. The FBA simulations using co-metabolism models comprising human host and a resident bacterium (Faecalibacterium prausnitzii or Bacteroides thetaiotamicron) indicated increased flux of 7-DHC with short-chain fructooligosaccharide (scFOS) or inulin supplementation. We observed around 2-fold increase in flux compared to the baseline. Biosynthesis of 7-DHC was primarily modulated through acetate, pyruvate and lactate secreted by the bacterium. We observed diverse mechanisms and dose dependent responses. We extended this assessment to 119 resident bacteria and investigated the metabolites profiles with prebiotics supplementation. In summary, the current study suggests the potential use of applying prebiotics in enhancing 7-DHC biosynthesis. Furthermore, performance of the different gut bacteria with prebiotic supplementation for secreted metabolites profile is reported. These results may be useful to design future clinical studies.
Highlights
Vitamin D is important in multiple health conditions
We assessed the impact of prebiotic supplementation on the intermediates of vitamin D3 biosynthesis pathway using human-gut microorganism co-metabolism models representing vitamin D3 deficient conditions
We examined two widely used prebiotics, inulin and short-chain fructooligosaccharide (scFOS) for each human-Faecalibacterium prausnitzii and human-Bacteroides thetaiotamicron models
Summary
Vitamin D is important in multiple health conditions. Vitamin D deficiency is prevalent globally even with exposure to adequate sunlight. The study by Holick and coworkers has shown that there is around 75% reduction in cutaneous 7-DHC levels resulting in proportionate decrease in vitamin D3 synthesis even with the exposure to sunlight[9]. Another factor leading to reduced biosynthesis of vitamin D3 is the skin melanin content. Higher melanin content results in reduced cutaneous synthesis of vitamin D35,10 In addition to these factors, post burn scar tissue has been shown to contain around 40% less 7-DHC and in the absence of supplementation such patients developed vitamin D deficiency[7,11].
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