Natural Compounds Modulating Bitter Taste Receptors: Implications for Multisystem Health and Disease

Bitter taste receptors (TAS2Rs), a subfamily of G protein-coupled receptors, have been recently recognized for their regulatory roles beyond gustation. They are widely expressed in the oral cavity, gastrointestinal (GI) tract, respiratory system, cardiovascular system, endocrine organs, reproductive tissues, and nervous system, playing crucial roles in immune modulation, metabolic homeostasis, microbiota interactions, and cancer progression. This review systematically summarizes the physiological functions and implications of TAS2Rs across multiple organ systems and microbial environments, emphasizing their roles in health. Specifically, we highlight the key role of TAS2R38 in maintaining oral microbiota balance and preventing dental caries. TAS2Rs are abundantly expressed in the GI tract. They regulate gut microbiota, promote hormone secretion, maintain intestinal barrier function, and influence metabolic processes. TAS2Rs and their subtypes play key roles in various tissues, regulating immune responses, cell signaling, and organ function, such as TAS2R38 in respiratory defense, TAS2R14 in cardiovascular regulation and metabolic control, TAS2R14 and TAS2R43 in reproductive health. Natural compounds can regulate health by influencing different subtypes of TAS2Rs, either promoting or inhibiting their activity. Recent studies suggest that TAS2Rs could serve as promising therapeutic targets for many diseases. Understanding the intricate interactions between TAS2Rs and diverse physiological pathways may pave the way for regulating appetite and metabolism, dietary intervention.