SPLTRAK Abstract Submission
Impact of Solitary Chemosensory Cells and TRPM5 on Murine Airway and Intestinal Microbiota
Vijay R. Ramakrishnan1, Jennifer M. Kofonow2, Thad Vickery1, Eric D. Larson1, Catherine B. Anderson1, Daniel N. Frank2
1Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO, United States
2Division of Infectious Disease, University of Colorado School of Medicine, Aurora, CO, United States

The human microbiome is increasingly recognized as a contributor to health and disease. Large interpersonal variability has been observed in studies of the human airway microbiome and can be partially attributed to differences in diet and environmental influence. However, host factors governing microbial colonization are of significant interest. Nasal solitary chemosensory cells (SCCs), and their lower airway and gut homologues (brush and tuft cells, respectively), have been recently observed to exhibit numerous immune properties. These cells are defined by their expression of Transient Receptor Potential Cation Channel Subfamily M member 5 (TRPM5) and require the transcription factor Skn-1a/Pou2f3 for development. In the present study, we examined upper airway and gut microbiota colonization in TRPM5-deficient and Skn-1a/Pou2f3-deficient mice using 16S rRNA gene sequencing. Immunohistochemistry and PCR were used to document the presence or absence of tissue-specific expression of TRPM5 and chemosensory markers in knockout and wild type mice. In gut, we found alterations in several bacterial taxa. TRPM5-deficient mice exhibited more Firmicutes and less Proteobacteria and Candidate-Division-TM7 at the phylum level, and less Helicobacter at the genus level. Skn-1a/Pou2f3-deficient mice were colonized with more Proteobacteria. In the nasal cavity, substantially lower bacterial biomass was recovered, limiting statistical comparisons. This study supports the immune regulatory capability of SCCs, indicates a role for chemosensory pathways in regulation of microbiota colonizing luminal surfaces, and suggests that SCCs may do this using TRPM5-independent pathways in addition to canonical taste transduction.    Funded by NIDCD K23DC014747 (VRR)