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.