TRPV4 deletion remodels the gut microbiota and increases colonic ammonia levels.

AIMS: The transient receptor potential vanilloid 4 ion channel is widely expressed in the gastrointestinal tract and contributes to epithelial barrier regulation, mechanosensation and innate immune signaling. However, its role in shaping gut microbiota composition and intestinal metabolic homeostasis remains unclear. This study aimed to determine whether deletion of TRPV4 influences gut microbial composition and intestinal ammonia levels. MATERIALS AND METHODS: Fecal microbiota from wild type and TRPV4 knockout mice were analyzed using taxonomic profiling and microbial diversity approaches. Alpha diversity and beta diversity metrics were used to evaluate microbial richness, evenness, phylogenetic diversity and community structure. Ammonia concentration and pH were measured in cecal and colonic contents. KEY FINDINGS: Phylogenetic diversity differed significantly between wild type and TRPV4 knockout mice whereas microbial richness and evenness were not altered. Beta diversity analysis revealed marked differences in microbial community composition between genotypes. The ratio of Bacillota to Bacteroidetes was reduced by approximately 50 % in TRPV4 knockout mice due to decreased Bacillota and increased Bacteroidetes abundance. In addition, TRPV4 knockout mice exhibited significantly elevated ammonia levels in both the colon and cecum compared with wild type mice. SIGNIFICANCE: Deletion of TRPV4 alters gut microbial community structure and intestinal nitrogen metabolism without affecting overall microbial richness or evenness. These findings identify TRPV4 as a novel regulator of gut microbiota composition and metabolic homeostasis and suggest that ion channel dependent signaling contributes to the regulation of gut microbial ecology and metabolite balance.