Activation of Extraoral Bitter Taste Receptors by Herbs and Spices in the Regulation of Incretin Signaling and Glucose Metabolism

Bitter compounds in plants, originally evolved as chemical defenses, are retained within the dry matrices of spices and culinary herbs, where they constitute a chemically diverse pool of potential ligands for bitter taste receptors (TAS2Rs) expressed along the gastrointestinal tract. Beyond their role in oral taste perception, TAS2Rs are increasingly recognized as extraoral chemosensory receptors capable of modulating intestinal physiology. Evidence suggests that activation of specific TAS2Rs by bitter phytochemicals can influence glucose transporter activity and stimulate the release of enteroendocrine hormones, including glucagon-like peptide-1 and cholecystokinin, thereby engaging established pathways involved in appetite regulation and glucose homeostasis. These shared downstream effects may explain why structurally diverse bitter phytochemicals often produce convergent metabolic outcomes. Framing bitter-receptor signaling within known enteroendocrine mechanisms highlights an underexplored opportunity to leverage herbs and spices as dietary modulators of metabolic function. Incorporating naturally bitter plant foods into dietary patterns may offer a simple, sustainable, and culturally adaptable approach to support metabolic health.