Diet-derived microbial metabolites modulate stress-responsive gene expression in germ-free zebrafish

Abstract

The gut microbiome plays a pivotal role in overall host health, yet the extent at which diet-derived microbial metabolites affect neurodevelopment and inflammation remains unclear. Here, we employed the robogut bioreactor system seeded with faecal samples from two healthy paediatric donors to generate microbial communities exposed to four different diets: low-fibre Western, high-fibre Western, Mediterranean, and Yanomami, as well as three fibre supplements: fruit and vegetable fibre, cereal fibre, and resistant starch fibre. Metabolites produced by these microbial communities were isolated and applied to germ-free zebrafish ( Danio rerio ) embryos to assess their effects on neurodevelopment and inflammatory gene expression under basal and stress-induced conditions. Despite minimal changes in microbial composition across diets and fibre sources, significant differences in short-chain fatty acid concentrations were observed. , Under basal conditions, metabolite treatments had limited effects on the expression of neural and inflammatory genes. Under stress conditions, metabolites from any diet mitigated stress-induced bdnf expression, suggesting a possible modulatory role of microbial metabolites on stress responses. Overall, these findings highlight the resilience of microbial communities to dietary changes and underscore the importance of microbial metabolite output and its donor-specific nature in influencing host neurodevelopment and immune responses.