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 a “natural experiment” opportunity to study dysgeusia due to its high prevalence in 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 dysfuncton(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 receptor (TLR)2 and TLR4, were also downregulated, suggesting chronic inflammation. These findings support a model of sustained dysregulated epithelial turnover for the impaired taste in LC-D. Saliva-based single-cell approaches offer promising tools for future diagnostics and mechanistic studies of taste systems.