Provitamin D₃ modulation through prebiotics supplementation: simulation based assessment

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.