Single-Cell Transcriptomic Analysis of Salivary Epithelial Cells Reveals Large-Scale Dysregulation in Bitter Taste Dysfunction.

Taste dysfunction, or dysgeusia, is a frequent symptom associated with infections and systemic diseases, yet its cellular and molecular basis remains poorly understood. The COVID-19 pandemic provided an opportunity to study dysgeusia as a "natural experiment" due to its high prevalence in those with acute and long COVID (LC). We investigated salivary epithelial cells (SECs) using single-cell RNA sequencing to elucidate molecular changes underlying taste dysfunction in LC. Functional enrichment analysis of SEC transcriptomes from individuals with bitter taste dysfunction (LC-D) revealed downregulation of genes involved in cytoskeletal dynamics and taste cell-nerve synapse assembly. Further, specific Type II and III taste receptor genes, critical for bitter taste perception, were reduced. Microbial defense markers such as Toll-like receptors TLR2 and TLR4 were also downregulated, suggesting chronic inflammation. These findings support a model of sustained dysregulated epithelial turnover due to impaired taste in LC-D. Saliva-based single-cell approaches offer promising tools for future diagnostics and mechanistic studies of taste systems.