Metabolic diseases such as type 2 diabetes and obesity pose a significant global health burden. Plant-based diets, including vegan diets, are linked to favorable metabolic outcomes, yet the underlying mechanisms remain unclear. In a randomized trial involving 21 pairs of identical twins, we investigated the effects of vegan and omnivorous diets on the host metabolome, immune system, and gut microbiome. Vegan diets induced significant shifts in serum and stool metabolomes, cytokine profiles, and gut microbial composition. Notably, vegan diet subjects exhibited elevated serum glycine levels despite lower dietary glycine intake, linked to reduced abundance of the gut pathobiont Bilophila wadsworthia. Functional studies demonstrated that B. wadsworthia metabolizes glycine via the glycine reductase pathway and modulates host glycine availability. Removing B. wadsworthia from gnotobiotic mice elevated glycine levels and improved metabolic markers. These findings reveal a previously underappreciated mechanism by which the gut microbiota regulates host metabolic status through diet.

The authors have declared no competing interest.

NCT05297825

This study was funded by the Vogt Foundation.

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Participants were recruited through the Stanford Twin Registry.The study was approved annually by the Stanford University Human Subjects Committee.

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