Bitter Taste Signaling is a Whole Body Health Event

For sweet, salty, sour, and umami flavours, the tongue has only one type of receptor. For bitter compounds, the human tongue possesses at least 25 different chemoreceptors—and most of these bitter receptor types have multiple genetic variants, resulting in considerable individuality in responsivity to bitter substances. Though our understanding of bitter receptor function is limited, bitter receptors may have evolved to discourage the ingestion of toxins. However, their presence in many non-oral tissues and functional variability suggests that their significance to health goes far beyond taste perception.

Bitter ‘taste’ receptors have been found in immune cells, the brain, airways, skin, liver, kidneys, testes, ovaries, nasal sinuses, heart, thyroid gland, bones, breasts, pancreatic beta cells, and intestines. For this reason, bitter receptors may be useful molecular targets in immune, metabolic, and endocrine conditions.

Specifically:

• Neutrophils appear to express several bitter receptors, and in concert with other signalling inputs, these interactions can result in increased or decreased neutrophil migration.
• Body mass index has been found to correlate significantly with immune reactivity in colonic mucosal cells expressing the T2R38 receptor, as yet the most widely researched bitter receptor.
• Bitter receptors may be involved in clearing surface microorganisms and limiting bacterial biofilm formation. In human sinus epithelium, activation of the T2R38 bitter receptor generates nitric oxide as a local bactericide.
• Bitter receptors have been discovered in multiple brain structures, and some bitter molecules are able to cross the blood-brain barrier
• Genetic expression of particular bitter receptors has been linked to risk for Parkinson’s disease, schizophrenia, and possibly also for breast cancer.
• Bitter receptor polymorphisms have been found to modify risk for altered glucose and insulin metabolism, cardiovascular disease, colorectal cancer, rhinosinusitis, infection with gram-negative bacteria, gingivitis, and dental caries.
• Gut protection from parasitic infection may be partly orchestrated by bitter receptor responses.
• In aortic and pulmonary muscle, bitter receptor ligands have shown relaxant effects.
• Cardiac muscle cells express at least five bitter receptors, and bitter compounds have been found to influence aortic, systolic, and ventricular blood pressures.

In this review, the authors detail mechanisms through which bitter receptor ligands may affect innate immunity, digestive secretion, thyroid hormone production, smooth muscle contraction, the glycaemic response, and other diverse functions. They also describe genetic polymorphisms in bitter receptors and their health effects in humans and animals.

Reference:

Lu P, Zhang CH, Lifshitz LM, ZhuGe R. Extraoral bitter taste receptors in health and disease. J Gen Physiol 2017;149(2):181-197.