Bitter Taste Receptor Mechanisms in Human Health

Bitter taste receptors (TAS2Rs) are a family of G protein-coupled receptors originally characterised in gustatory cells but now recognised to have widespread extra-oral expression. They play key roles in detecting potentially harmful compounds and orchestrating physiological responses in the respiratory, gastrointestinal and endocrine systems. Upon binding of bitter ligands, TAS2Rs couple to taste-specific G proteins and activate phospholipase Cβ2, leading to inositol 1,4,5-trisphosphate formation and elevation of intracellular calcium. These signals may induce membrane hyperpolarisation, smooth muscle relaxation, hormone secretion and modulation of inflammatory pathways. Genetic variation in TAS2Rs underpins inter-individual differences in bitter sensitivity, dietary preferences and disease susceptibility. The translational potential of targeting these receptors spans novel bronchodilators, modulators of gastrointestinal motility and agents to influence glucose homeostasis, illustrating their broad relevance to human health.

Research from Nature Portfolio

Studies of vertebrate chemoreceptor repertoires across more than 1,500 genomes have revealed lineage-specific expansions and losses of bitter taste receptor genes, indicating that diet and habitat have driven the evolution of TAS2R diversity. This work provides an evolutionary framework for understanding human variation in bitter receptor complement and its impact on toxin detection and metabolic regulation. In parallel, machine-learning classifiers trained on physicochemical descriptors have been shown to predict bitterness from chemical structure with over 80 % accuracy, offering a high-throughput in silico approach to identify candidate bitter ligands for therapeutic development.

Bitter Taste Receptor Mechanisms in Human Health publication trend

The graph below shows the total number of articles in bitter taste receptor mechanisms in human health across all publications each year (not limited to Nature Index journals).

Technical terms

TAS2R: A member of the bitter taste receptor family, each functioning as a G protein-coupled receptor sensitive to a range of bitter compounds.

G protein-coupled receptor (GPCR): A cell-surface receptor that transduces extracellular signals into intracellular responses via coupling to heterotrimeric G proteins.

Agonist: A substance that binds to a receptor and elicits a physiological response.

Bronchodilation: The process of relaxing airway smooth muscle to widen airways and improve airflow.

Enteroendocrine L cells: Hormone-secreting cells in the intestinal mucosa that release incretins such as glucagon-like peptide-1 in response to nutrients.

References

1. Diversity and evolution of the vertebrate chemoreceptor gene repertoire. Nature Communications (2024).
2. BitterDB database analysis plus cell stiffness screening identify flufenamic acid as the most potent TAS2R14-based relaxant of airway smooth muscle cells for therapeutic bronchodilation. Theranostics (2024).
3. The Cellular and Molecular Basis of Bitter Tastant-Induced Bronchodilation. PLOS Biology (2013).
4. Molecular Mechanisms of Bitter and Sweet Taste Transduction*. Journal of Biological Chemistry (2001).
5. Targeting extra-oral bitter taste receptors modulates gastrointestinal motility with effects on satiation. Scientific Reports (2015).
6. Bitter Taste Receptors Influence Glucose Homeostasis. PLOS ONE (2008).
7. Bitter or not? BitterPredict, a tool for predicting taste from chemical structure. Scientific Reports (2017).
8. Genetic Background of Taste Perception, Taste Preferences, and Its Nutritional Implications: A Systematic Review. Frontiers in Genetics (2019).