Clinical Presentation of Chronic Abacterial Prostatitis Shows No Association with TAS2R38 Taster Status

The immune system uses a variety of chemoreceptors to detect potential pathogens and initiate a targeted defense response against them [1]. In some cases, the immune and taste systems use the same chemoreceptors, in particular the bitter taste receptors from the taste receptor family 2 (T2R) [2]. These are G protein-coupled receptors, which were originally found in the type 2 receptor taste cells of the tongue, but have since been found in numerous other tissues, especially the respiratory tract [2, 3]. Chemosensory tuft cells are seen as key contributors to this process [4‒6]. They act as sentinels at entry sites, using canonical taste transduction pathways to detect harmful stimuli and trigger protective responses [5, 7‒9].

Recent studies have identified T2Rs as a novel mechanism of innate pathogen recognition in the airways [10‒12]. These receptors are expressed in various respiratory cells and regulate innate immune defense processes in both mice and humans [13‒16]. Within this family, the T2R isoform 38 protein (T2R38), mainly found in the cilia of the nose and paranasal sinuses, plays a key role in antigen detection [16, 17]. Sensitivity to the bitter compounds phenylthiocarbamide and 6-propyl-2-thiouracil (PTU/PROP) is linked to TAS2R38 and varies between individuals. Three single nucleotide polymorphisms form two common haplotypes, PAV and AVI [18, 19]. The PAV haplotype is associated with tasting phenylthiocarbamide/PTU, while AVI is linked to nontasting, resulting in three genotypes: PAV/PAV (“super taster”), PAV/AVI (“taster”), and AVI/AVI (“non-taster”). Taste strip tests are commonly used to determine this status [20, 21].

TAS2R38 had a significant influence on pathogen detection, the course of an upper respiratory tract infection, and the development of chronic sinusitis [16, 17]. Further studies have shown that a failure of chemorecognition of TAS2R38, were associated with a higher risk of chronic sinusitis and nasal polyps [22‒24]. TAS2R38 was particularly involved in the detection of gram-negative bacteria such as Pseudomonas aeruginosa by detecting bacterial quorum sensing molecules and other metabolites at mucosal interfaces and modulating the immune response to these pathogens [25, 26].

Further studies have shown increased expression of TAS2R38 in the bladder urothelium and detrusor, suggesting a potential link to recurrent urinary tract infections (UTIs) and overactive bladder symptoms [27, 28]. TAS2R38 in epithelia also contributes to the recognition of Escherichia coli and regulation of immune responses via receptor-specific mechanisms [29].

Although comprehensive studies on its role in UTIs are limited, involvement seems likely, particularly given the role of urethral tuft cells in defending against uropathogenic bacteria and regulating urogenital inflammation [26]. Expression of multiple T2R receptors has been identified in cholinergic urethral brush cells, where activation by heat-inactivated uropathogenic E. coli triggers the micturition reflex and induces neurogenic inflammation [9, 30, 31].

Chronic prostatitis (CP) is a common disorder with lifetime prevalences ranging from 1.8 to 8.2% [32, 33]. Conditions causing neuropathic pain and those increasing susceptibility to UTIs are considered risk factors [34]. Individuals with factors enabling retrograde bacterial ascent into the urethra and prostate, as well as a history of urethritis due to sexually transmitted infections (STIs), appear more prone to developing CP [34‒36]. It is important to distinguish prostatitis from other causes of pelvic pain, such as benign prostate hyperplasia, interstitial cystitis, and other sources of dysuria [37, 38].

The National Institutes of Health (NIH) has divided the condition into four categories: acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS) (category III), and asymptomatic inflammatory prostatitis (category IV) [38]. Type IIIA, which has inflammatory features in the ejaculate, and type IIIB, which does not, are further divisions of category III [38]. CP/CPPS accounts for about 90% of cases of CP. At least 3 months of prostatic pain without conclusive microbiological results are required [32, 38‒40]. It is clinically important to accurately differentiate between type II and type III, as the former necessitates antibiotic treatment while the latter requires nonantibiotic, symptom-focused management [39].

As mentioned, urogenital infections contribute significantly to CP/CPPS pathogenesis [34‒36]. The UPOINTS classification system of the European Association of Urology (EAU) enables phenotypic stratification across seven domains (urinary, psychosocial, organ-specific, infection, neurological/systemic, tenderness, sexual) and supports individualized management [41‒43]. This study aims to evaluate the association between TAS2R38 taster status and CP/CPPS, including symptom severity, recurrent UTIs, and microbiological findings.

As part of our specialized consultation for pelvic pain/CP, this prospective study investigated 360 patients referred to our tertiary university department from December 2016 to October 2025 due to suspected CP.

Prior to inclusion, each patient provided his written informed consent to participate in our study. The Institutional Ethics Committee of Justus-Liebig-University Giessen also granted a positive approval (protocol code 55/13, date of approval: 4 November 2013). Men who did not fulfill the diagnostic criteria for CP/CPPS (n = 108) were excluded from the study population. The study group was made up of 252 individuals with CP/CPPS. The control group consisted of 79 age-matched subjects without a history of current or previous prostate diseases and without recurrent UTIs.

Every participant underwent a comprehensive andrological assessment, which involved a systematic review of their medical history, validated questionnaires for lower urinary tract symptoms (International Prostate Symptom Score, IPSS), erectile dysfunction (International Index of Erectile Function, IIEF), and CP (National Institutes of Health Chronic Prostatitis Symptom Index, NIH-CPSI), a physical examination, analysis of sex hormones, a 2-glass urine test, and further semen analysis [39, 40]. Phenotyping was accomplished by using the categories of UPOINTS system [41]. Ultrasonography was employed to evaluate the volumes of the prostate and testicles, as per clinical recommendations [44, 45]. Irregularities were also documented.

Routine blood draws were performed on every patient to assess serum levels of prostate-specific antigen (PSA), estrogen, testosterone (normal range: 300–1,000 ng/dL), C-reactive protein (CRP), and estradiol. If a lower testosterone level was discovered, the levels of prolactin, sex hormone-binding globulin, albumin, follicle-stimulating hormone, luteinizing hormone, and albumin were measured simultaneously using standard laboratory procedures in the central laboratory of Giessen University Hospital (ADVIA and ADVIA Centaur, Siemens Health Care). Leukocyturia was detected using a urine dipstick and an automated quantitative urine particle analyzer (Cobas u 411, Roche Diagnostics GmbH). The individual conducting the tests was unaware of the source of the material.

To rule out a bacterial pathogen as the source of pelvic pain, conventional cultures and PCR tests for sexually transmitted pathogens were conducted on first-void urine, post-prostatic massage urine, and ejaculate samples. Bacteriospermia was defined as a bacterial count exceeding 1,000 colony-forming units (CFUs) per milliliter of ejaculate [46]. In the case of urine samples, a bacterial count of at least 1,000 CFUs per ml was considered significant [47].

A blind analysis of the semen was performed within an hour of collection, following WHO 2010 and WHO 2021 guidelines, with the methodologies for basic semen parameters remaining consistent [48, 49]. After disinfecting the glans and foreskin and adhering to patient instructions, samples were gathered at the clinic by means of masturbation into a sterile container. All patients underwent testing of their urine (first-void urine, urine post-prostatic massage) and semen for STIs (Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and received bacterial cultures to exclude the presence of infections [50].

During standard processing, the concentration of leukocytes that tested positive for peroxidase was assessed (Leucoscreen, FertiPro). Furthermore, in each semen sample (Demeditec Diagnostics GmbH), polymorphonuclear elastase, which indicates local inflammation, was quantified in cell-free seminal plasma with an enzyme-linked immunoassay. Concentrations of the inflammatory cytokine interleukin-8 (IL-8) were measured using the cytometric bead array method (BD Biosciences, San Jose, CA, USA). Neutral α-glucosidase and fructose (total enzymatic activity) amounts were measured using spectrophotometric techniques, as described in [51].

The presence of a functional TAS2R38 receptor was determined by a taste strip test. For this test, the subject first received an untreated cellulose strip, which served as a negative control and elicited no taste sensation. The patient then received a strip containing 6-n-propylthiouracil (Eisco Labs, Honeoey Falls, NY, USA), which, as a natural ligand, promptly elicited a bitter taste sensation in the presence of a functional receptor [52, 53]. The division into tasters and nontasters was soley based on taste perception, without any further subdivision in the intensity of taste perception. A further distinction of the super-tasters was not performed, as the indication of the intensity of the bitter taste would be too subjective.

The statistical analysis was conducted using SPSS 30 for Windows (IBM GmbH, Ehningen, Germany). An a priori size calculation was performed using a one-way ANOVA power analysis. A p value <0.05 was considered significant. The data were tested for normal distribution using the Kolmogorov-Smirnov test and Quantile-Quantile plot.

Since most data were not normally distributed, the Mann-Whitney U test was applied. Mann-Whitney U test was used to compare patients depending on their taster status with various parameters. A value of p < 0.05 was considered statistically significant. Since multiple clinical and laboratory parameters were compared between the groups, the Holm-Bonferroni correction was applied as an adjustment for multiple comparisons.

Multivariate regression modeling was used to examine the association between the results of the taste test and various seminal inflammatory parameters, sperm concentration, CRP and PSA, and the CPSI total score. Only non-missing data were included in the modeling exercise using a forward stepwise process. A value of p < 0.05 was considered statistically significant.

To calculate a sufficient number of participants to reliably detect relevant differences between tasters and nontasters, an a priori sample size calculation was performed (Table 1). We conducted a one-way ANOVA with a single power of 0.95, a value of 0.25, and a significance level of 0.05. This resulted in a minimum study population size of 210 participants, demonstrating that the study was sufficiently powered.

The detailed clinical and demographic findings are shown in Table 2. With a median age of 39, the patients were aged between 20 and 84 years. Type IIIB CP was found in 85.7% of the patients, while 14.3% had type IIIA CP. Among those assessed, the proportion of tasters was 55.95%, while nontasters accounted for 44.05%.

The study group exhibited a medium level of lower urinary tract symptoms, indicated by a median score of 10 points on the International Prostate Symptom Score (IPSS). The median score for the International Index of Erectile Function (IIEF) was 27 points, falling within the normal range. The Chronic Prostatitis Symptom Index (NIH-CPSI) from the National Health Institute indicated a moderate symptom burden associated with CP, with median scores of 12 points for pain (CPSI-I), 3 points for urinary tract symptoms (CPSI-II), and 9 points for the impact on quality of life (CPSI-III). Unfortunately, not all patients were able to complete the questionnaires due to language barriers. Although a validated questionnaire in the patient’s native language was used where available, these were not available for some of our patients (especially Kurdish and Pashto speakers). Additionally, those who did not engage in sexual activity were not able to complete the IIEF-5 questionnaire in a meaningful way. Missing data did not lead to exclusion from the study.

Among our study population, the organ-specific domain was affected most frequently (96.42%), followed by the urinary (78.17%) and sexual (57.93%) domains. In contrast, recurrent urogenital infections were identified in only a minority of patients (4.76%). The median number of impacted domains was three from a total of seven.

The mean testicular volume measured was 15.0 mL, which falls within the normal range [44]. The median prostate volume, which was 21.0 mL [45], is similarly true.

The laboratory parameters were within normal limits, with median values of total testosterone at 436 ng/dL, PSA at 0.69 ng/mL, estradiol at 30 pg/mL, and C-reactive protein (CRP) at 0.5 mg/L.

Table 3 presents the WHO lower reference limits for the basic semen variables alongside the semen parameters of the patients. The study population showed no signs of inflammatory processes, as demonstrated by the median values of all evaluated semen parameters within the cohort falling within the normal range, especially for the seminal markers of inflammation IL-8, elastase, and peroxidase-positive leukocytes. Due to the fact that the ejaculate volume was sometimes insufficient, not every parameter could be assessed in every case.

Each sample type (first-void urine, post-prostatic massage urine, ejaculate) underwent microbiological analysis using conventional culture and STI-PCR. There were only n = 4 patients with a positive STI in our study population. In 2 patients, Ureaplasma urealyticum and Mycoplasma hominis were detected simultaneously, while a co-infection with Mycoplasma hominis and Mycoplasma genitalium was detected once. All STI-positive patients received appropriate antibiotic therapy with subsequent eradication testing via STI-PCR and a follow-up visit after 6–12 months. In all affected patients, the symptoms of CP persisted despite successful pathogen eradication, ultimately leading to a diagnosis of type III prostatitis.

Online supplementary Table S1A presents the pathogens identified in the first-void urine, categorized by microbiological culture and STI-PCR. In our study cohort, which had undergone extensive antibiotic pretreatment, the conventional culture yielded positive results for only 51 patients. The identified pathogens were primarily either contaminations or constituents of the normal flora, exhibiting a predominantly low bacterial count ranging from 100 to 1,000 CFU per milliliter.

In the same way, online supplementary Table S1B presents the microbiological findings from urine collected after prostatic massage. The same patients showed a positive STI-PCR as in the first-void urine analysis, with two STI pathogens detected simultaneously in 1 patient.

The results for the ejaculate are shown in online supplementary Table 1C. Again, only very few pathogens were identified by culture (n = 49) and STI-PCR (n = 4). This time, in 3 patients with positive STI-PCR double infections could be detected: Mycoplasma hominis and Ureaplasma urealtyicum were simultaneously detected twice, Mycoplasma hominis and Mycoplasma hominis once.

Table 4 compares the clinical characteristics between tasters and nontasters. To test for significant differences, both groups were compared using the Mann-Whitney U test; a p < 0.05 was considered significant.

No significant differences were found between the two groups with regard to age, blood biochemistry, questionnaire results, or most ejaculate parameters. Only seminal elastase and serum levels of CRP showed a significant difference, with elevated levels in the tasters. After applying the Holm-Bonferroni correction, no result remains significant (α = 0.05). The initially found significant differences therefore should be considered a type I error. This also seems plausible, as higher values for both parameters were found in the tasters, which would contradict the initial hypothesis.

To compare the microbiological results, patients with at least one positive culture and at least one positive STI-PCR in one of the three sample types (first-void urine, post-prostate massage urine, ejaculate) were compared. Again, no statistically significant differences were found between the two groups.

Table 5 shows a univariate and multivariate analysis between taster status and sperm concentration as an important fertility marker, the parameters of seminal inflammation (leukocytes in ejaculate, levels of elastase and IL-8), the CPSI total score as a marker for symptom burden, microbiological results and the PSA and CRP levels in serum. A positive microbiological culture in at least one of the three sample types (first-void urine, post-void urine, ejaculate) again leads to classification in the “positive culture” group. The same procedure was followed in the case of a positive STI test. PSA and CRP were chosen as surrogate parameters for prostatic inflammation. There was no significant association with any of the parameters examined, except for seminal plasma elastase and serum CRP levels in the univariate analysis. A p < 0.05 was considered statistically significant.

Table 6 compares the parameters collected from patients with CP to those of the control group. The Mann-Whitney U test was used to test for significant differences; a p value <0.05 was considered significant. As expected, a significant difference was found in the scores of the IPSS and CPSI questionnaires, with higher scores in the prostatitis group. No significant differences were found regarding the other biochemical and seminal parameters. In particular, the percentage of nontasters based on the TAS2R38 was almost identical in both groups.

As a continuation of our previous publications [54], our study is the first to investigate the role of TAS2R38 receptor functionality in the clinical presentation of CP NIH type III. Previous studies have shown that nontaster status or lack of chemoreception of the receptor is associated with a higher risk of upper respiratory tract infections and the development of chronic sinusitis [16, 17, 22, 23]. Evidence indicates that the TAS2R38 receptor is particularly involved in the detection of Pseudomonas aeruginosa and thus performs a function in the antigen recognition of the innate immune system [25, 26]. Another study was also able to demonstrate the chemodetection of Escherichia coli by the receptor, which makes it interesting for a potential role in UTIs [31]. At mucosal interfaces in the digestive system and the urogenital tract, it has been demonstrated that various bitter receptors of the TAS2R family can detect quorum sensing molecule and other bacterial metabolites and lead to activation of the innate immune system [25, 26]. UTIs are considered a risk factor for the development of chronic abacterial prostatitis [34], and thus a connection with the functionality of the TAS2R38 receptor is conceivable. Increased expression of TAS2R38 in the urothelium and detrusor muscle was also detected, which, in addition to activation of the immune system and local inflammation, also provides direct protection against the penetration of pathogens into the urogenital system by triggering the micturition reflex [26‒28]. However, assuming that the TAS2R38-mediated defense reactions are associated with urethral tuft cells, it is rather unlikely that abacterial processes are influenced by the taster status.

In our study population, 44% of the subjects in the prostatitis group were nontasters and 43% in the control group; this essentially corresponds to the expected distribution between tasters and nontasters in a Western European cohort. Other studies have found a similar distribution in the general population of European populations, with nontaster rates varying between 24.8 and 53.5% [55‒57].

Based on our study data, we could not detect an association between the functionality of the TAS2R38 receptor and the clinical presentation of CP type III. Neither the symptom burden of the questionnaires used, nor the examined ejaculate parameters and PSA values, nor the results of the microbiology showed a significant difference between tasters and nontasters. Only seminal elastase and serum CRP levels showed a significant difference between the two groups, but with higher values in the taster group, which, in view of our initial hypothesis, is more likely a statistical coincidence. After Holm-adjustment of the p values, no corresponding significance could be demonstrated, suggesting a type I error. Also, no significant differences in biochemistry and seminal parameters were found between the prostatitis group and the control group, except for the IPSS and CPSI scores. Univariate analysis only showed a difference between tasters and nontasters for seminal elastase and serum CRP levels; however, this difference was no longer detectable in multivariate analysis. Taken together, this provides little evidence of a link between the functionality of the taste receptor and the clinical presentation of chronic abacterial prostatitis.

A prominent feature of our population is the low rate of positive conventional bacterial culture and STI-PCR results in the samples examined: the STI-PCR showed no pathogen detection in 98% of all three sample types (first-void urine, post-prostate massage urine, ejaculate), and the classical culture also showed no pathogen growth in 79–87%. If a bacterium was detected, it was usually due to contamination with the skin or urethral flora. Only very rarely was a potentially uropathogenic bacterium such as Escherichia coli or Klebsiella oxytoca detected, and then only in low numbers of around 1,000 bacteria/mL, so that even these detections were considered insignificant. One explanation for this could be the frequent prior treatment by the referring physician. Although not systematically recorded by us, the vast majority of patients had received antibiotic therapy in their history, so that an initial link to a urogenital infection was no longer detectable at the time of presentation. This factor could have had a significant impact on the detection rate of a pathogen and represents a clear limitation of our study in the interpretation of the microbiological results. Another limitation stems from the fact that we did not test for all potential sexually transmitted pathogens. Our panel deliberately focused on pathogens that are readily detectable in urine and ejaculate and are described in the literature as typical STIs associated with chronic bacterial prostatitis [33‒35]. Testing for other sexually transmitted pathogens, such as syphilis or the human immunodeficiency virus, was not included. Based on the UPOINTS classification, only 4.76% of the subjects showed an affected infectious domain, indicating that recurrent UTIs play only a minor role in the cohort, at least with regard to phenotyping.

A clear limitation of our study is the single-center data collection and the lack of systematic recording of prior antibiotic treatment. Furthermore, testing for the functionality of the TAS2R38 receptor was only based on the taste test and not via genetic testing. While the taste test is very good at detecting a complete loss of chemoreception [52], it cannot objectively distinguish between reduced sensitivity and normal function. This could lead to differences in the corresponding subgroups that could not be investigated using this method. While the division into tasters and nontasters is a pragmatic approach and easy to apply in practice, it does also not allow for a distinction between heterozygous and homozygous genotypes. This lack of differentiation could prevent the detection of subtle genotype-phenotype associations, potentially influencing the negative study result. Follow-up studies addressing the same research question could employ genetic testing.

The aim of our study was to investigate whether abacterial prostatitis is associated with the taster status; therefore, our study cohort consisted exclusively of patients with chronic type III prostatitis.

While an acute urogenital infection can be identified in the medical history of many patients with this condition as the initial onset of pelvic pain, by definition no relevant pathogens are detected during the course of the disease. Since abacterial prostatitis is promoted by many different factors (UPOINTS), it is unlikely to depend an acute urogenital infection alone. In our opinion, however, only bacterial UTIs may be influenced by TAS2R38, possibly through urethral tuft cells. Therefore, it is not surprising that we found no correlation between taster status and abacterial prostatitis. From a clinical perspective, routine testing for receptor functionality cannot be recommended.

However, in a population with chronic bacterial prostatitis type II, a corresponding correlation is much more likely in future studies in which a relevant pathogen is found when the patient is presented. For such patient population, a repeat study with a similar design would be worthwhile in the future, possibly expanding the testing beyond the taste test to include human genetic analysis to determine the genotype. As mentioned above, recruiting a suitable cohort from the patients referred to us was not possible, presumably due to the extensive antibiotic pretreatment by the referring physicians, as hardly any cases of chronic bacterial prostatitis were found. Similarly, the connection we suspect between the functioning chemoreception of the TAS2R38 receptor and UTIs, analogous to respiratory tract infections, is plausible but has not yet been confirmed by several independent studies.

The results of our studies show that the taste status of TAS2R38 in patients with chronic abacterial prostatitis type III had no association with symptom severity, the ejaculate parameters examined, or the serum levels of PSA and CRP.

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Ethics Committee of Justus-Liebig-University Giessen (protocol code 55/13, date of approval: 4 November 2013). Written informed consent was obtained from all subjects involved in the study.

Florian M. Wagenlehner was a member of the journal’s Editorial Board at the time of submission. The remaining authors have no conflicts of interest.

This study was funded by the German Research Foundation (DFG, 544054869 to K.D.).

Jens Rosellen: formal analysis, investigation, data curation, and writing – original draft. Adrian Pilatz: data curation, investigation, and writing – review and editing. Hans-Christian Schuppe and Undraga Schagdarsurengin: investigation and writing – review and editing. Lea Hofmann: conceptualization, formal analysis, investigation, writing – original draft, and visualization. Klaus Deckmann: conceptualization, formal analysis, investigation, data curation, writing – original draft, visualization, and project administration. Florian Wagenlehner: conceptualization, writing – review and editing, and supervision. All authors have read and agreed to the published version of the manuscript.

Klaus Deckmann and Florian Wagenlehner contributed equally to this work.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author [J.R.] ([email protected]) upon request.