TAAR5 GENETIC DELETION ALTERS GUT MICROBIOTA IN MICE

The trace amine-associated receptors (TAARs) are a novel class of G protein-coupled receptors with high pharmacological potential. In previous studies, we demonstrated that TAAR5, an olfactory receptor, is linked to the regulation of emotional behaviors and hippocampal neurogenesis. Given that trace amines are emerging as potential mediators of the gut-brain axis, we investigated whether TAAR5 deletion influences the gut microbiota, potentially contributing to the observed neural and behavioral effects. Using 16S rRNA sequencing, we conducted a comprehensive analysis of the gut microbiome in TAAR5-knockout (TAAR5-KO) and wild-type (WT) mice. While alpha-diversity remained unchanged, beta-diversity analysis revealed a significant separation between the genotypes. TAAR5-KO mice displayed a distinct taxonomic signature characterized by a significant enrichment of psychobiotic and butyrate-producing taxa, including Lachnospiraceae, Lactobacillus, and Akkermansia, alongside a reduction in Prevotellaceae. This specific microbial and metabolic profile is widely associated in the literature with anti-inflammatory states, enhanced production of neuroactive metabolites, and antidepressant effects. Our findings provide the first evidence that TAAR5 is a key regulator of gut microbiome composition and function. We propose that the absence of TAAR5 shapes a microbial ecosystem that may contribute to the previously reported serotonergic modulation, enhanced neurogenesis, and antidepressant-like phenotype, positioning TAAR5 as a novel link between chemosensation, the gut microbiome, and brain function.