| Summary: | Transient receptor potential (TRP) channel family proteins are sensors for pain, which sense a variety of thermal and noxious chemicals. Sensory neurons innervating the gut abundantly express TRPA1 and TRPV1 channels and are in close proximity of gut microbes. Emerging evidence indicates a bi-directional gut–brain cross-talk in several entero-neuronal pathologies; however, the direct evidence of TRP channels interacting with gut microbial populations is lacking. Herein, we examine whether and how the knockout (KO) of TRPA1 and TRPV1 channels individually or combined TRPA1/V1 double-knockout (dKO) impacts the gut microbiome in mice. We detect distinct microbiome clusters among the three KO mouse models versus wild-type (WT) mice. All three TRP-KO models have reduced microbial diversity, harbor higher abundance of Bacteroidetes, and a reduced proportion of <i>Firmicutes</i>. Specifically distinct arrays in the KO models are determined mainly by <i>S24-7</i>, <i>Bacteroidaceae</i>, <i>Clostridiales</i>, <i>Prevotellaceae, Helicobacteriaceae, Rikenellaceae,</i> and <i>Ruminococcaceae</i>. A1KO mice have lower <i>Prevotella, Desulfovibrio, Bacteroides</i>, <i>Helicobacter</i> and higher <i>Rikenellaceae</i> and <i>Tenericutes</i>; V1KO mice demonstrate higher <i>Ruminococcaceae, Lachnospiraceae, Ruminococcus, Desulfovibrio</i> and <i>Mucispirillum</i>; and A1V1dKO mice exhibit higher <i>Bacteroidetes, Bacteroides</i> and <i>S24-7</i> and lower <i>Firmicutes, Ruminococcaceae, Oscillospira, Lactobacillus</i> and <i>Sutterella</i> abundance. Furthermore, the abundance of taxa involved in biosynthesis of lipids and primary and secondary bile acids is higher while that of fatty acid biosynthesis-associated taxa is lower in all KO groups. To our knowledge, this is the first study demonstrating distinct gut microbiome signatures in TRPA1, V1 and dKO models and should facilitate prospective studies exploring novel diagnostic/ therapeutic modalities regarding the pathophysiology of TRP channel proteins.
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