Environmental signals modify gut microbiome and metabolome enhancing neural plasticity through short-chain fatty acids

Gut microorganisms can thoroughly affect brain function in the host and their behavior. Since alteration of brain plasticity has been demonstrated upon motor, sensorial and social enrichment of the housing conditions, together with cognitive effects, we hypothesized that gut microbiota and metabolome could be altered by environmental stimuli, providing part of the missing link among environmental signals and brain effects. Metabolomic and metagenomic analysis of mice housed in different environmental conditions, standard and enriched, identified environment-specific metabolic profiles and sharp differences in the microbial community composition. We show that mice housed in an enriched environment have a reduction in gut bacterial richness and diversity indexes, and we identified a metabolomic fingerprint with the increase of formate and acetate and the decrease of bile salts. Our observation that mice treated with a mixture of formate and acetate recapitulate some of the brain plasticity effects induced by environmental enrichment, such as hippocampal neurogenesis, neurotrophin production and cognitive behaviors can be further exploited to decipher the mechanisms involved in experience-dependent brain plasticity.