The bitterness of genitourinary infections: Properties, ligands of genitourinary bitter taste receptors and mechanisms linking taste sensing to inflammatory processes in the genitourinary tract

Abstract

Background: Though, first identified in the gastrointestinal tract, bitter taste receptors are now believed to be ubiquitously expressed in several regions of the body, including the respiratory tract, where they play a critical role in sensing and clearance of excess metabolic substrates, toxins, debris, and pathogens. More recently, bitter taste receptor expression has been reported in cells, tissues and organs of the genitourinary (GU) system, suggesting that these receptors may play an integral role in mediating inflammatory responses to microbial aggression in the GU tract. However, the mechanisms, linking bitter taste receptor sensing with inflammatory responses are not exactly clear. Here, I review recent data on the properties and ligands of bitter taste receptors and suggest mechanisms of bitter taste receptor signaling in the GU tract, and the molecular pathways that link taste sensing to inflammatory responses in GU tract.

Method: Computer-aided search was conducted in Scopus, PubMed, Web of Science and Google Scholar for relevant peer-reviewed articles published between 1990 and 2018, investigating the functional implication of bitter taste receptors in GU infections, using the following keywords: extra-oral bitter taste receptors, bitter taste receptors, GU bitter taste receptors, kidney OR renal OR ureteral OR urethral OR bladder OR detrusor smooth muscle OR testes OR spermatozoa OR prostate OR vaginal OR cervix OR ovarian OR endometrial OR myometrial OR placenta OR cutaneous bitter taste receptors. To identify research gaps on etiopathogenesis of GU infections/inflammation, additional search was conducted using the following keywords: GU inflammatory signaling, GU microbes, GU bacteria, GU virus, GU protozoa, GU microbial metabolites, and GU infection. The retrieved articles were filtered and further screened for relevance according to the aim of the study. A narrative review was performed for selected literatures.

Results: Bitter taste receptors of the GU tract may constitute essential components of the pathogenetic mechanisms of GU infections/inflammation that are activated by microbial components, known as quorum sensing signal molecules. Based on accumulating evidences, indicating that taste receptors may signal downstream to activate inflammatory cascades, in addition to the nitric oxide-induced microbicidal effects produced upon taste receptor activation, it is suggested that the anti-inflammatory activities of bitter taste receptor stimulation are mediated via pathways involving the nuclear factor κB by downstream signaling of the metabolic and stress sensors, adenosine monophosphate-activated protein kinase and nicotinamide adenine dinucleotide-dependent silent mating type information regulation 2 homolog 1 (sirtuin 1), resulting to the synthesis of anti-inflammatory cytokines/chemokines, and antimicrobial factors, which ultimately, under normal conditions, leads to the elimination of microbial aggression.

Conclusions: GU bitter taste receptors may represent critical players in GU tract infections/inflammation. Bitter taste receptors may serve as important therapeutic target for treatment of a number of infectious diseases that affect the GU tract.

Keywords: Genitourinary bitter taste receptor; Genitourinary infection; Genitourinary inflammation; Inflammatory cascades.