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Provitamin D3 modulation through prebiotics supplementation: simulation based assessment.

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Area of Science:

  • Microbiome and Metabolism
  • Nutritional Biochemistry
  • Computational Biology

Background:

  • Vitamin D deficiency is a global health concern, exacerbated by reduced provitamin D3 (7-dehydrocholesterol, 7-DHC) levels.
  • Current strategies to combat deficiency include supplementation, food fortification, and probiotics, but endogenous production enhancement is underexplored.

Purpose of the Study:

  • To investigate the potential of dietary prebiotics to enhance 7-dehydrocholesterol (7-DHC) biosynthesis.
  • To elucidate the mechanistic details and constraints of 7-DHC biosynthesis using computational modeling.

Main Methods:

  • Flux Balance Analysis (FBA) simulations were employed using co-metabolism models of the human host and resident gut bacteria (e.g., Faecalibacterium prausnitzii, Bacteroides thetaiotamicron).
  • Simulations assessed the impact of short-chain fructooligosaccharide (scFOS) and inulin supplementation on 7-DHC flux.
  • Metabolite profiles and bacterial responses to prebiotics were analyzed across 119 resident bacteria species.

Main Results:

  • Prebiotic supplementation (scFOS, inulin) significantly increased 7-DHC biosynthesis flux by approximately two-fold compared to baseline.
  • Acetate, pyruvate, and lactate secreted by gut bacteria were identified as key modulators of 7-DHC biosynthesis.
  • Diverse mechanisms and dose-dependent responses were observed, with varied bacterial performance in metabolite profiles.

Conclusions:

  • Dietary prebiotics show promise as a strategy to enhance endogenous 7-dehydrocholesterol (7-DHC) biosynthesis.
  • Gut bacteria play a crucial role in mediating 7-DHC production in response to prebiotic intake.
  • Findings provide a basis for designing future clinical studies on prebiotic interventions for vitamin D precursor synthesis.