Home screening of taste and oral trigeminal function: a feasibility study.

PURPOSE: gustatory ability is a marker of health not routinely tested in the medical practice. The current study wants to assess whether taste strips can be useful to monitor taste function from home. METHODS: we performed simple sensory tests in lab setting vs. unassisted testing at home, and compared the results with self-reports ability to taste and smell. Using paper strips impregnated with sweet, bitter, salty, or sour tastants, and with two trigeminal stimuli (capsaicin, tannins) in high and low concentrations, we assessed gustatory and trigeminal function in 74 participants (47 women) in the lab, where paper strips were administered by an experimenter, and in 77 participants (59 women) at home, where they self-administered the test. RESULTS: we found that high (but not low) concentration taste strips are correctly identified by vast majority of participants. On average, taste identification, intensity and pleasantness scores did not differ for the 8 taste strips, while identification of capsaicin was significantly better in the lab. Taste identification scores correlated with intensity ratings in both settings (r = 0.56, in the lab, r = 0.48, at home, p < 0.005). Self-rated taste ability correlated with self-rated smell ability (r = 0.68, and r = 0.39, p ≤ 0.005), but not with scores in the strips test. CONCLUSION: home testing with impregnated taste strips is feasible, and can be used for telemedical purposes.

Molecular and Genetic Factors Involved in Olfactory and Gustatory Deficits and Associations with Microbiota in Parkinson's Disease.

Deficits in olfaction and taste are among the most frequent non-motor manifestations in Parkinson's disease (PD) that start very early and frequently precede the PD motor symptoms. The limited data available suggest that the basis of the olfactory and gustatory dysfunction related to PD are likely multifactorial and may include the same determinants responsible for other non-motor symptoms of PD. This review describes the most relevant molecular and genetic factors involved in the PD-related smell and taste impairments, and their associations with the microbiota, which also may represent risk factors associated with the disease.

Differences in Salivary Proteins as a Function of PROP Taster Status and Gender in Normal Weight and Obese Subjects.

Taste plays an important role in processes such as food choices, nutrition status and health. Salivary proteins contribute to taste sensitivity. Taste reduction has been associated with obesity. Gender influences the obesity predisposition and the genetic ability to perceive the bitterness of 6-n-propylthiouracil (PROP), oral marker for food preferences and consumption. We investigated variations in the profile of salivary proteome, analyzed by HPLC-ESI-MS, between sixty-one normal weight subjects (NW) and fifty-seven subjects with obesity (OB), based on gender and PROP sensitivity. Results showed variations of taste-related salivary proteins between NW and OB, which were differently associated with gender and PROP sensitivity. High levels of Ps-1, II-2 and IB-1 proteins belonging to basic proline rich proteins (bPRPs) and PRP-1 protein belonging to acid proline rich proteins (aPRPs) were found in OB males, who showed a lower body mass index (BMI) than OB females. High levels of Ps-1 protein and Cystatin SN (Cyst SN) were found in OB non-tasters, who had lower BMI than OB super-tasters. These new insights on the role of salivary proteins as a factor driving the specific weight gain of OB females and super-tasters, suggest the use of specific proteins as a strategic tool modifying taste responses related to eating behavior.

Effect of the rs2821557 Polymorphism of the Human Kv1.3 Gene on Olfactory Function and BMI in Different Age Groups.

The sense of smell plays an important role in influencing the eating habits of individuals and consequently, their body weight, and its impairment has been associated with modified eating behaviors and malnutrition problems. The inter-individual variability of olfactory function depends on several factors, including genetic and physiological ones. In this study, we evaluated the role of the Kv1.3 channel genotype and age, as well as their mutual relationships, on the olfactory function and BMI of individuals divided into young, adult and elderly groups. We assessed olfactory performance in 112 healthy individuals (young n = 39, adult n = 36, elderly n = 37) based on their TDI olfactory score obtained through the Sniffin' Sticks test and their BMI. Participants were genotyped for the rs2821557 polymorphism of the human gene encoding Kv1.3 channels, the minor C allele of which was associated with a decreased sense of smell and higher BMIs compared to the major T allele. The results show that TT homozygous subjects obtained higher TDI olfactory scores and showed lower BMIs than CC homozygous subjects, in all age groups considered. Furthermore, the positive effect of the T allele on olfactory function and BMI decreased with increasing age. The contribution of the genetic factor is less evident with advancing age, while the importance of the age factor is compensated for by genetics. These results show that genetic and physiological factors such as age act to balance each other.

Time-frequency analysis of gustatory event related potentials (gERP) in taste disorders.

In taste disorders, the key to a correct diagnosis and an adequate treatment is an objective assessment. Compared to psychophysical tests, EEG-derived gustatory event-related potentials (gERP) could be used as a less biased measure. However, the responses identified using conventional time-domain averaging show a low signal-to-noise ratio. This study included 44 patients with dysgeusia and 59 healthy participants, who underwent a comprehensive clinical examination of gustatory function. gERPs were recorded in response to stimulation with two concentrations of salty solutions, which were applied with a high precision gustometer. Group differences were examined using gERP analyzed in the canonical time domain and with Time-Frequency Analyses (TFA). Dysgeusic patients showed significantly lower scores for gustatory chemical and electrical stimuli. gERPs failed to show significant differences in amplitudes or latencies between groups. However, TFA showed that gustatory activations were characterized by a stronger power in controls than in patients in the low frequencies (0.1-4 Hz), and a higher desynchronization in the alpha-band (8-12 Hz). Hence, gERPs reflect the altered taste sensation in patients with dysgeusia. TFA appears to enhance the signal-to-noise ratio commonly present when using conventional time-domain averaging, and might be of assistance for the diagnosis of dysgeusia.

Gene Methylation Affects Salivary Levels of the Taste Buds' Trophic Factor, Gustin Protein.

The salivary protein, Gustin/carbonic anhydrase VI, has been described as a trophic factor responsible for the growth of taste buds. We found, in a genetically homogeneous population, that the polymorphism rs2274333 (A/G) of the Gustin gene is crucial for the full functionality of the protein and is associated with taste sensitivity. However, other studies have failed to find this evidence. Here, we verified if Gustin gene methylation can affect the salivary levels of the protein, also concerning the polymorphism rs2274333 and PROP bitter responsiveness. The Gustin gene methylation profiling and the quantification of the Gustin salivary levels were determined in sixty-six volunteers genotyped for the polymorphism rs2274333 (A/G) (Ser90Gly in the protein sequence). The fungiform papillae density was also determined. The results confirm our earlier observations by showing that AA genotypes had a greater density of fungiform taste papillae, whereas the GG genotypes showed a lower density. We also found variations in the protein levels in the three genotype groups and an inverse relationship between Gustin gene methylation and the salivary levels of the protein, mostly evident in AA and ST volunteers, i.e., in volunteers who would be carriers of the functional isoform of the protein. These findings could justify the conflicting data in the literature.

Automated identification of the genetic variants of TAS2R38 bitter taste receptor with supervised learning.

Several studies were focused on the genetic ability to taste the bitter compound 6-n-propylthiouracil (PROP) to assess the inter-individual taste variability in humans, and its effect on food predilections, nutrition, and health. PROP taste sensitivity and that of other chemical molecules throughout the body are mediated by the bitter receptor TAS2R38, and their variability is significantly associated with TAS2R38 genetic variants. We recently automatically identified PROP phenotypes with high precision using Machine Learning (mL). Here we have used Supervised Learning (SL) algorithms to automatically identify TAS2R38 genotypes by using the biological features of eighty-four participants. The catBoost algorithm was the best-suited model for the automatic discrimination of the genotypes. It allowed us to automatically predict the identification of genotypes and precisely define the effectiveness and impact of each feature. The ratings of perceived intensity for PROP solutions (0.32 and 0.032 mM) and medium taster (MT) category were the most important features in training the model and understanding the difference between genotypes. Our findings suggest that SL may represent a trustworthy and objective tool for identifying TAS2R38 variants which, reducing the costs and times of molecular analysis, can find wide application in taste physiology and medicine studies.

A Supervised Learning Regression Method for the Analysis of the Taste Functions of Healthy Controls and Patients with Chemosensory Loss.

In healthy humans, taste sensitivity varies widely, influencing food selection and nutritional status. Chemosensory loss has been associated with numerous pathological disorders and pharmacological interventions. Reliable psychophysical methods are crucial for analyzing the taste function during routine clinical assessment. However, in the daily clinical routine, they are often considered too time-consuming. We used a supervised learning (SL) regression method to analyze with high precision the overall taste statuses of healthy controls (HCs) and patients with chemosensory loss, and to characterize the combination of responses that would best predict the overall taste statuses of the subjects in the two groups. The random forest regressor model allowed us to achieve our objective. The analysis of the order of importance of each parameter and their impact on the prediction of the overall taste statuses of the subjects in the two groups showed that salty (low-concentration) and sour (high-concentration) stimuli specifically characterized healthy subjects, while bitter (high-concentration) and astringent (high-concentration) stimuli identified patients with chemosensory loss. Although the present results require confirmation in studies with larger samples, the identification of such distinctions should be of interest to the health system because they may justify the use of specific stimuli during the routine clinical assessments of taste function and thereby reduce time and cost commitments.

Emotional responses to taste and smell stimuli: Self-reports, physiological measures, and a potential role for individual and genetic factors.

Taste and olfaction elicit conscious feelings by direct connection with the neural circuits of emotions that affects physiological responses in the body (e.g., heart rate and skin conductance). While sensory attributes are strong determinants of food liking, other factors such as emotional reactions to foods may be better predictors of consumer choices even for products that are equally-liked. Thus, important insights can be gained for understanding the full spectrum of emotional reactions to foods that inform the activities of product developers and marketers, eating psychologist and nutritionists, and policy makers. Today, self-reported questionnaires and physiological measures are the most common tools applied to study variations in emotional perception. The present review discusses these methodological approaches, underlining their different strengths and weaknesses. We also discuss a small, emerging literature suggesting that individual differences and genetic variations in taste and smell perception, like the genetic ability to perceive the bitter compound PROP, may also play a role in emotional reactions to aromas and foods.

A supervised learning regression method for the analysis of oral sensitivity of healthy individuals and patients with chemosensory loss.

The gustatory, olfactory, and trigeminal systems are anatomically separated. However, they interact cognitively to give rise to oral perception, which can significantly affect health and quality of life. We built a Supervised Learning (SL) regression model that, exploiting participants' features, was capable of automatically analyzing with high precision the self-ratings of oral sensitivity of healthy participants and patients with chemosensory loss, determining the contribution of its components: gustatory, olfactory, and trigeminal. CatBoost regressor provided predicted values of the self-rated oral sensitivity close to experimental values. Patients showed lower predicted values of oral sensitivity, lower scores for measured taste, spiciness, astringency, and smell sensitivity, higher BMI, and lower levels of well-being. CatBoost regressor defined the impact of the single components of oral perception in the two groups. The trigeminal component was the most significant, though astringency and spiciness provided similar contributions in controls, while astringency was most important in patients. Taste was more important in controls while smell was the least important in both groups. Identifying the significance of the oral perception components and the differences between the two groups provide important information to allow for more targeted examinations supporting both patients and healthcare professionals in clinical practice.

Automated Classification of 6-n-Propylthiouracil Taster Status with Machine Learning.

Several studies have used taste sensitivity to 6-n-propylthiouracil (PROP) to evaluate interindividual taste variability and its impact on food preferences, nutrition, and health. We used a supervised learning (SL) approach for the automatic identification of the PROP taster categories (super taster (ST); medium taster (MT); and non-taster (NT)) of 84 subjects (aged 18-40 years). Biological features determined from subjects were included for the training system. Results showed that SL enables the automatic identification of objective PROP taster status, with high precision (97%). The biological features were classified in order of importance in facilitating learning and as prediction factors. The ratings of perceived taste intensity for PROP paper disks (50 mM) and PROP solution (3.2 mM), along with fungiform papilla density, were the most important features, and high estimated values pushed toward ST prediction, while low values leaned toward NT prediction. Furthermore, TAS2R38 genotypes were significant features (AVI/AVI, PAV/PAV, and PAV/AVI to classify NTs, STs, and MTs, respectively). These results, in showing that the SL approach enables an automatic, immediate, scalable, and high-precision classification of PROP taster status, suggest that it may represent an objective and reliable tool in taste physiology studies, with applications ranging from basic science and medicine to food sciences.

Associations between Sweet Taste Sensitivity and Polymorphisms (SNPs) in the TAS1R2 and TAS1R3 Genes, Gender, PROP Taster Status, and Density of Fungiform Papillae in a Genetically Homogeneous Sardinian Cohort.

Individual differences in sweet taste sensitivity can affect dietary preferences as well as nutritional status. Despite the lack of consensus, it is believed that sweet taste is impacted by genetic and environmental variables. Here we determined the effect of well-established factors influencing the general taste variability, such as gender and fungiform papillae density, specific genetic variants (SNPs of TAS1R2 and TAS1R3 receptors genes), and non-specific genetic factors (PROP phenotype and genotype), on the threshold and suprathreshold sweet taste sensitivity. Suprathreshold measurements showed that the sweet taste response increased in a dose-dependent manner, and this was related to PROP phenotype, gender, rs35874116 SNP in the TAS1R2 gene, and rs307355 SNP in the TAS1R3 gene. The threshold values and density of fungiform papillae exhibited a strong correlation, and both varied according to PROP phenotype. Our data confirm the role of PROP taste status in the sweet perception related to fungiform papilla density, show a higher sweet sensitivity in females who had lower BMI than males, and demonstrate for the first time the involvement of the rs35874116 SNP of TAS1R2 in the sweet taste sensitivity of normal weight subjects with body mass index (BMI) ranging from 20.2 to 24.8 kg/m2. These results may have an important impact on nutrition and health mostly in subjects with low taste ability for sweets and thus with high vulnerability to developing obesity or metabolic disease.

A Simple Taste Test for Clinical Assessment of Taste and Oral Somatosensory Function-The "Seven-iTT".

Taste dysfunctions may occur, for example, after viral infection, surgery, medications, or with age. In clinical practice, it is important to assess patients' taste function with rapidity and reliability. This study aimed to develop a test that assesses human gustatory sensitivity together with somatosensory functions of astringency and spiciness. A total of 154 healthy subjects and 51 patients with chemosensory dysfunction rated their gustatory sensitivity. They underwent a whole-mouth identification test of 12 filter-paper strips impregnated with low and high concentrations of sweet, sour, salty, bitter (sucrose, citric acid, NaCl, quinine), astringency (tannin), and spiciness (capsaicin). The percentage of correct identifications for high-concentrated sweet and sour, and for low-concentrated salty, bitter and spicy was lower in patients as compared with healthy participants. Interestingly, a lower identification in patients for both astringent concentrations was found. Based on the results, we proposed the Seven-iTT to assess chemo/somatosensory function, with a cut-off of 6 out of 7. The test score discriminated patients from healthy controls and showed gender differences among healthy controls. This quantitative test seems to be suitable for routine clinical assessment of gustatory and trigeminal function. It also provides new evidence on the mutual interaction between the two sensory systems.

Daily Exposure to a Cranberry Polyphenol Oral Rinse Alters the Oral Microbiome but Not Taste Perception in PROP Taster Status Classified Individuals.

Diet and salivary proteins influence the composition of the oral microbiome, and recent data suggest that TAS2R38 bitter taste genetics may also play a role. We investigated the effects of daily exposure to a cranberry polyphenol oral rinse on taste perception, salivary proteins, and oral microbiota. 6-n-Propylthiouracil (PROP) super-tasters (ST, n = 10) and non-tasters (NT, n = 10) rinsed with 30 mL of 0.75 g/L cranberry polyphenol extract (CPE) in spring water, twice daily for 11 days while consuming their habitual diets. The 16S rRNA gene sequencing showed that the NT oral microbiome composition was different than that of STs at baseline (p = 0.012) but not after the intervention (p = 0.525). Principal coordinates analysis using unweighted UniFrac distance showed that CPE modified microbiome composition in NTs (p = 0.023) but not in STs (p = 0.096). The intervention also altered specific salivary protein levels (α-amylase, MUC-5B, and selected S-type Cystatins) with no changes in sensory perception. Correlation networks between oral microbiota, salivary proteins, and sensory ratings showed that the ST microbiome had a more complex relationship with salivary proteins, particularly proline-rich proteins, than that in NTs. These findings show that CPE modulated the oral microbiome of NTs to be similar to that of STs, which could have implications for oral health.

Changes of Taste, Smell and Eating Behavior in Patients Undergoing Bariatric Surgery: Associations with PROP Phenotypes and Polymorphisms in the Odorant-Binding Protein OBPIIa and CD36 Receptor Genes.

Bariatric surgery is the most effective long-term treatment for severe obesity and related comorbidities. Although patients who underwent bariatric surgery report changes of taste and smell perception, results from sensory studies are discrepant and limited. Here, we assessed taste and smell functions in 51 patients before, one month, and six months after undergoing bariatric surgery. We used taste strip tests to assess gustatory function (including sweetness, saltiness, sourness, umaminess, bitterness and oleic acid, a fatty stimulus), the "Sniffin' Sticks" test to assess olfactory identification and the 3-Factor Eating Questionnaire to assess eating behavior. We also explored associations between these phenotypes and flavor-related genes. Results showed an overall improvement in taste function (including increased sensitivity to oleic acid and the bitterness of 6-n-propylthiouracil (PROP)) and in olfactory function (which could be related to the increase in PROP and oleic acid sensitivity), an increase in cognitive restraint, and a decrease in disinhibition and hunger after bariatric surgery. These findings indicate that bariatric surgery can have a positive impact on olfactory and gustatory functions and eating behavior (with an important role of genetic factors, such PROP tasting), which in turn might contribute to the success of the intervention.

Olfactory Function in Patients with Inflammatory Bowel Disease (IBD) Is Associated with Their Body Mass Index and Polymorphism in the Odor Binding-Protein (OBPIIa) Gene.

Smell strongly contributes to food choice and intake, influencing energy balance and body weight; its reduction or loss has been related to malnutrition problems. Some patients with inflammatory bowel disease (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC), are underweight, while others are overweight. Some studies suggest that changes in eating habits could be linked to specific disorders of the olfactory functions. We assessed the olfactory performance in 199 subjects (healthy control (HC) n = 99, IBD n = 100), based on the olfactory Threshold, Discrimination and Identification score (TDI score), measured with the "Sniffin' Sticks" test. Subjects were genotyped for the rs2590498 polymorphism of the OBPIIa gene. IBD patients showed both a slightly, but significantly, lower olfactory function and a higher BMI compared to HC subjects. Threshold (in both population) and Discrimination (in IBD patients) olfactory score were affected by the OBPIIa genotype. BMI was influenced by both health status and OBPIIa genotype. A lower olfactory function may delay the satiety sensation and thus increase meal duration and body weight in IBD patients. However, the AA genotype of the OBPIIa seems to "protect" IBD patients from more severe olfactory dysfunction.

Time Course of Salivary Protein Responses to Cranberry-Derived Polyphenol Exposure as a Function of PROP Taster Status.

Astringency is a complex oral sensation, commonly experienced when dietary polyphenols interact with salivary proteins. Most astringent stimuli alter protein levels, which then require time to be replenished. Although it is standard practice in astringency research to provide breaks in between stimuli, there is limited consensus over the amount of time needed to restore the oral environment to baseline levels. Here we examined salivary protein levels after exposure to 20 mL of a model stimulus (cranberry polyphenol extract, 0.75 g/L CPE) or unsweetened cranberry juice (CJ), over a 10 min period. Whole saliva from healthy subjects (n = 60) was collected at baseline and after 5 and 10 min following either stimulus. Five families of proteins: basic proline-rich proteins (bPRPs); acidic proline-rich proteins (aPRPs); histatins; statherin; and S-type cystatins, were analyzed in whole saliva via HPLC-low resolution-ESI-IT-MS, using the area of the extracted ion current (XIC) peaks. Amylase was quantified via immunoblotting. In comparison to baseline (resting), both stimuli led to a rise in levels of aPRPs (p < 0.000) at 5 min which remained elevated at 10 min after stimulation. Additionally, an interaction of PROP taster status and time was observed, wherein super-tasters had higher levels of amylase in comparison to non-tasters after stimulation with CJ at both timepoints (p = 0.014-0.000). Further, male super-tasters had higher levels of bPRPs at 5 min after stimulation with both CJ and CPE (p = 0.015-0.007) in comparison to baseline. These data provide novel findings of interindividual differences in the salivary proteome that may influence the development of astringency and that help inform the design of sensory experiments of astringency.

Electrophysiological Responses from the Human Tongue to the Six Taste Qualities and Their Relationships with PROP Taster Status.

Taste buds containing receptor cells that primarily detect one taste quality provide the basis for discrimination across taste qualities. The molecular receptor multiplicity and the interactions occurring between bud cells encode information about the chemical identity, nutritional value, and potential toxicity of stimuli before transmitting signals to the hindbrain. PROP (6-n-propylthiouracil) tasting is widely considered a marker for individual variations of taste perception, dietary preferences, and health. However, controversial data have been reported. We present measures of the peripheral gustatory system activation in response to taste qualities by electrophysiological recordings from the tongue of 39 subjects classified for PROP taster status. The waveform of the potential variation evoked depended on the taste quality of the stimulus. Direct relationships between PROP sensitivity and electrophysiological responses to taste qualities were found. The largest and fastest responses were recorded in PROP super-tasters, who had the highest papilla density, whilst smaller and slower responses were found in medium tasters and non-tasters with lower papilla densities. The intensities perceived by subjects of the three taster groups correspond to their electrophysiological responses for all stimuli except NaCl. Our results show that each taste quality can generate its own electrophysiological fingerprint on the tongue and provide direct evidence of the relationship between general taste perception and PROP phenotype.

Taste Changes in Patients with Inflammatory Bowel Disease: Associations with PROP Phenotypes and polymorphisms in the salivary protein, Gustin and CD36 Receptor Genes.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract resulting from interactions among various factors with diet being one of the most significant. IBD-related dietary behaviors are not clearly related to taste dysfunctions. We analyzed body mass index (BMI) and perception of six taste qualities and assessed effects of specific taste genes in IBD patients and healthy subjects (HC). BMI in IBD patients was higher than in HC subjects. Taste sensitivity to taste qualities was reduced in IBD patients, except for sour taste, which was higher than in HC subjects. Genetic variations were related to some taste responses in HC subjects, but not in IBD patients. Frequencies of genotype AA and allele A in CD36 polymorphism (rs1761667) were significantly higher in IBD patients than in HC subjects. The taste changes observed could be explained by the oral pathologies and microbiome variations known for IBD patients and can justify their typical dietary behaviors. The lack of genetic effects on taste in IBD patients indicates that IBD might compromise taste so severely that gene effects cannot be observed. However, the high frequency of the non-tasting form of CD36 substantiates the fact that IBD-associated fat taste impairment may represent a risk factor for IBD.

Human Tongue Electrophysiological Response to Oleic Acid and Its Associations with PROP Taster Status and the CD36 Polymorphism (rs1761667).

The perception of fat varies among individuals and has also been associated with CD36 rs1761667 polymorphism and genetic ability to perceive oral marker 6-n-propylthiouracil (PROP). Nevertheless, data in the literature are controversial. We present direct measures for the activation of the peripheral taste system in response to oleic acid by electrophysiological recordings from the tongue of 35 volunteers classified for PROP taster status and genotyped for CD36. The waveform of biopotentials was analyzed and values of amplitude and rate of potential variation were measured. Oleic acid stimulations evoked positive monophasic potentials, which represent the summated voltage change consequent to the response of the stimulated taste cells. Bio-electrical measurements were fully consistent with the perceived intensity during stimulation, which was verbally reported by the volunteers. ANOVA revealed that the amplitude of signals was directly associated, mostly in the last part of the response, with the CD36 genotypes and PROP taster status (which was directly associated with the density of papillae). The rate of potential variation was associated only with CD36, primarily in the first part of the response. In conclusion, our results provide direct evidence of the relationship between fat perception and rs1761667 polymorphism of the CD36 gene and PROP phenotype.