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.

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.

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.

The Implications of Taste and Olfaction in Nutrition and Health.

Taste and olfaction are sensory modalities that act synergistically to orchestrate the behaviors essential for survival, such as interactions with the environment, nutrient-rich food identification, and the avoidance of noxious substances [...].

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.

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.

Olfactory Sensitivity Is Associated with Body Mass Index and Polymorphism in the Voltage-Gated Potassium Channels Kv1.3.

Smell strongly contributes to food choice and its hedonistic evaluation. A reduction or loss of smell has been related to malnutrition problems, resulting in excessive weight loss or gain. Voltage-gated potassium channels Kv1.3 are widely expressed in the olfactory bulb, and contribute mainly to the value of the resting membrane potential and to the frequency of action potentials. Mutations in the Kv1.3 gene are associated with alterations in glycemic homeostasis and olfactory sensitivity. We evaluated the olfactory performance in 102 healthy subjects and its association with BMI and polymorphism in the human Kv1.3 gene. Olfactory performance, based on the olfactory threshold, discrimination and identification scores and their summed score (TDI), was measured using the "Sniffin' Sticks" test. Subjects were genotyped for the rs2821557 polymorphism of the Kv1.3 gene, whose major allele T was associated with a super-smeller phenotype, lower plasma glucose levels and resistance to diet-induced obesity as compared with the minor allele C. Based on the Kv1.3 genotype, the TDI and I olfactory scores obtained by the subjects were the following: TT > TC > CC. Subjects who were TT homozygous or heterozygous exhibited lower BMIs and reached higher olfactory scores than those with the CC genotype. The results were sex-dependent: heterozygous females performed better than heterozygous males. These findings show an inverse relationship between olfactory function and BMI, and a significant effect of the Kv1.3 genotypes on the olfactory functions and on the BMIs of the subjects. Finally, they suggest that the sex-related differences in the olfactory function can be partially ascribed to the Kv1.3 gene's polymorphism.

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.

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.

A polymorphism in the human gene encoding OBPIIa affects the perceived intensity of smelled odors.

Among the factors that contribute to the physiological variability of the olfactory function of individuals, an important role seems to be played by the OBPs present in the mucus that bathes the ciliated terminals of the olfactory sensory neurons, facilitating the access of odorants to the olfactory receptors. It was recently highlighted that the rs2590498 polymorphism in the odor binding-protein (OBPIIa) gene it is associated with the olfactory threshold in healthy individuals. Aim of this study was to evaluate: 1) the presence of a relationship between the threshold olfactory performance of healthy subjects and the intensity with which they perceive the smelled odorants, and 2) the effect of the rs2590498 polymorphism of the OBPIIa gene on perceived intensity. We found a positive correlation between threshold olfactory and perceived intensity, and that AA homozygous subjects reported a perceived intensity higher than heterozygous and GG homozygous subjects. By showing a positive effect of the rs2590498 polymorphism of the hOBPIIa gene on the intensity perceived, these results suggest that it allows a larger number of molecules in an odorous mixture to reach the olfactory receptors.

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.

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.

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.

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.

Effect of the rs2890498 polymorphism of the OBPIIa gene on the human ability to smell single molecules.

Most odors of foods and drinks are mixtures of molecules. By means of the coupled Gas Chromatography-Olfactometry (GC-O) technique, single components of flavor mixtures can be separated, identified and verbally evaluated by subjects. The number of single molecules smelled by subjects during GC-O analysis (i.e., the number of odor-active compounds) was previously found to be linearly correlated with odor Threshold (T) score. Using the "Sniffin' Sticks" test, the same subjects were classified as normosmic or hyposmic. Hydrophobic odorants are captured and transported through the mucus layer by the odorant binding proteins (OBPs), particularly expressed in the olfactory cleft and associated with the olfactory function. In this study, subjects were genotyped for the rs2590498 (A/G) polymorphism of the OBPIIa gene, whose major allele A is associated with a higher olfactory sensitivity as compared to the minor allele G. One-way ANOVA showed a significant effect of the genotype of the OBPIIa locus on the: a) T score; b) number of odor-active compounds smelled; c) intensity perceived when sniffing the complex odor of banana. In conclusion, the threshold olfactory performance, but also the individual ability to smell single molecules, can be attributed, partly at least, to the rs2590498 polymorphism of the OBPIIa gene.

Genetic variants of TAS2R38 bitter taste receptor associate with distinct gut microbiota traits in Parkinson's disease: A pilot study.

The non-tasting form of the bitter taste receptor, TAS2R38, has been shown as a genetic risk factor associated with the development of Parkinson's disease (PD). Specific taste receptors that are expressed in the lower gastrointestinal tract may respond to alteration in gut microbiota composition, detecting bacterial molecules, and regulate immune responses. Given the importance of brain-gut-microbiota axis and gene-environment interactions in PD, we investigate the associations between the genetic variants of TAS2R38 and gut microbiota composition in 39 PD patients. The results confirm that the majority of PD patients have reduced sensitivity to 6-n-propylthiouracil (PROP) and are carriers of at least one non-functional TAS2R38 AVI haplotype. Moreover, we found this correlation to be associated with a reduction in bacteria alpha-diversity with a predominant reduction of Clostridium genus. We hypothesised that the high frequency of the non-taster form of TAS2R38 associated with a diminuition of Clostridium bacteria in PD might determine a reduction in the activation of protective signalling-molecules useful in preserving gut homeostasis. This pilot study, by identifying a decrease in specific bacteria associated with a reduced sensitivity to PROP, adds essential information that opens new avenues of research into the association of PD microbiota composition and sensory modification.

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.

"Smelling and Tasting" Parkinson's Disease: Using Senses to Improve the Knowledge of the Disease.

Among non-motor manifestations of Parkinson's Disease (PD), peripheral, sensory symptoms are particularly relevant. Smell dysfunction starts very early and frequently precedes the PD motor symptoms by years (being often a cue to the diagnosis). Moreover, olfactory system could be, together with gut, one of those peripheral sites where PD pathology first develops. Unlike smell loss, the relationship between PD and taste impairment is far less established. It can start early in the course of the disease but more frequently appears in advanced stages, in parallel with the advent of MCI, likely reflecting cortical involvement. Among PD patients has been demonstrated an increase in the frequency of the non-tasters for PROP (prototypical gustatory stimulus, 6- n-propylthiouracil), a genetically determined bitter taste which is mediated by TAS2RS38 receptor, and a significant increase of the recessive non-testing variant of this receptor. TAS2R38 receptors are expressed also in other tissues, such as in the epithelia of the gut and nasal cavities, where they can influence epithelial immunity ad its interaction with microbiota. Those pieces of evidence suggest that not only systematic assessment of taste and smell can be of a remarkable help for clinicians in the early diagnosis, but also that understanding the mechanisms of sensory involvement in PD could increase the knowledge of the pathophysiology of the disease.