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.

Does presbygeusia really exist? An updated narrative review.

This review critically assessed the existence of presbygeusia, i.e., the impairment in taste perception occurring in the elderly, as a natural part of the aging process and its potential clinical implications. Several factors might contribute to age-related taste alterations (TAs), including structural changes in taste buds, alterations in saliva composition, central nervous system changes, and oral microbiota dysbiosis. A comprehensive literature review was conducted to disentangle the effects of age from those of the several age-related diseases or conditions promoting TAs. Most of the included studies reported TAs in healthy elderly people, suggesting that presbygeusia is a relatively frequent condition associated with age-related changes in the absence of pathological conditions. However, the impact of TAs on dietary preferences and food choices among the elderly seems to be less relevant when compared to other factors, such as cultural, psychological, and social influences. In conclusion, presbygeusia exists even in the absence of comorbidities or drug side effects, but its impact on dietary choices in the elderly is likely modest.

The Obese Taste Bud study: Objectives and study design.

AIMS: Taste modifies eating behaviour, impacting body weight and potentially obesity development. The Obese Taste Bud (OTB) Study is a prospective cohort study launched in 2020 at the University of Leipzig Obesity Centre in cooperation with the HI-MAG Institute. OTB will test the hypothesis that taste cell homeostasis and taste perception are linked to obesity. Here, we provide the study design, data collection process and baseline characteristics. MATERIALS AND METHODS: Participants presenting overweight, obesity or normal weight undergo taste and smell tests, anthropometric, and taste bud density (TBD) assessment on Day 1. Information on physical and mental health, eating behaviour, physical activity, and dental hygiene are obtained, while biomaterial (saliva, tongue swap, blood) is collected in the fasted state. Further blood samples are taken during a glucose tolerance test. A stool sample is collected at home prior to Day 2, on which a taste bud biopsy follows dental examination. A subsample undergoes functional magnetic resonance imaging while exposed to eating-related cognitive tasks. Follow-up investigations after conventional weight loss interventions and bariatric surgery will be included. RESULTS: Initial results show that glycated haemoglobin levels and age are negatively associated with TBD, while an unfavourable metabolic profile, current dieting, and vegan diet are related to taste perception. Olfactory function negatively correlates with age and high-density lipoprotein cholesterol. CONCLUSION: Initial findings suggest that metabolic alterations are relevant for taste and smell function and TBD. By combining omics data from collected biomaterial with physiological, metabolic and psychological data related to taste perception and eating behaviour, the OTB study aims to strengthen our understanding of taste perception in obesity.

Influence of Sodium Chloride on Human Bitter Taste Receptor Responses.

In the past, taste interactions between sodium chloride (NaCl) and bitter tastants were investigated in human sensory studies, and the suppression of bitterness by sodium was observed. It is currently not clear if this phenomenon occurs predominantly peripherally or centrally and if the effect is general or only particular bitter compounds are blocked. Therefore, the influence of NaCl at the receptor level was tested by functional expression assays using four out of ∼25 human bitter taste receptors together with prototypical agonists. It was observed that NaCl affected only the responses of particular bitter taste receptor-compound pairs, whereas other bitter responses remained unchanged upon variations of the sodium concentrations. Among the tested receptors, TAS2R16 showed a reduction in signaling in the presence of NaCl. This demonstrates that for some receptor-agonist pairs, NaCl reduces the activation at the receptor level, whereas central effects may dominate the NaCl-induced bitter taste inhibition for other substances.

Back to the water: Tongue morphology associated to contrasting lifestyles in two Andean frogs of the genus Telmatobius.

The evolution of the tongue in tetrapods is associated with feeding in the terrestrial environment. This study analyzes the tongue morphology of two closely related frog species, Telmatobius oxycephalus and T. rubigo, which exhibit contrasting feeding mechanisms. Telmatobius oxycephalus, a semi-aquatic species, relies on its tongue to capture terrestrial prey whereas T. rubigo, a secondarily aquatic species, uses suction feeding not involving the tongue. Through anatomical, histological and scanning electron microscopy analyses, we revealed remarkable differences in tongue morphology between these species. Telmatobius oxycephalus exhibits a well-developed tongue whose dorsal epithelium has numerous and slender filiform papillae. The epithelial cells of the papillae are protruded and have a complex array of microridges. In contrast, T. rubigo possesses a reduced tongue with flat and less numerous filiform papillae. The epithelial cells are completely flat and lack microridges. These findings highlight the remarkable adaptability of lingual morphology in Telmatobius to respond to the contrasting ecological niches and prey capture mechanisms. This study sheds light on the relationship between tongue shape and the different functional demands, contributing to our understanding of the evolution of prey capture mechanisms in amphibians.

[Research progress in functional regeneration methods and mechanisms of taste buds].

Gustation is one of the most important human senses. Taste dysfunctions, which may be due to aging, tongue cancer surgery, radiotherapy and chemotherapy, affect life quality. That is why the need for taste bud regeneration has received more attention. At present, research on development and renewal of taste cells provides a basis for taste bud regeneration; molecular mechanisms related to taste bud regeneration are being continuously uncoverd, aiding in the identification of more accurate targets for therapy. New methods such as nerve regeneration, tissue engineering, and cytokine therapy have emerged. The author reviews the mechanism and the latest methods of taste bud regeneration of lingual epithelium, aiming to open new horizions for the prevention and treatment of gustatory diseases, and provide theoretical references for its regeneration.

The gustin gene variation at rs2274333 and PROP taster status affect dietary fat perception: a stepwise multiple regression model study.

Gustin, a trophic factor for taste bud development, and its polymorphism at rs2274333 influence taste perception of 6-n-propylthiouracil (PROP) and fungiform papillae (FP) density. The PROP taster status affects dietary fat sensing and body composition. However, there is a paucity of research on the gustin genotype with dietary fat perception, PROP tasting ability, and body mass index (BMI). Thus, taste sensitivity to fat and bitterness was evaluated in 178 healthy individuals. The general labeled magnitude scale was used to determine suprathreshold taste intensity ratings, whereas the alternative forced choice approach was used to estimate the taste-sensing ability. The FP density was assessed by applying blue-colored food dye over the anterior region of the tongue. Restriction fragment length polymorphism was used to detect the genetic polymorphism (rs2274333) in the carbonic anhydrase VI (CA-VI) gene. Fisher's chi-square analysis showed that the CA-VI genotype and allelic frequencies significantly correlated (p<0.001) with the PROP taster status and BMI. Healthy individuals with AA genotypes of the CA-VI polymorphism and PROP super-tasters demonstrated stronger gustatory sensitivity for linoleic acid (LA) with greater FP density in comparison to individuals with AG/GG genotypes and other PROP taster groups. Stepwise forward multiple regression analysis indicates that BMI and PROP taster status significantly influence the LA sensing ability. The suprathreshold intensity rating for LA was also significantly impacted by PROP taster status and CA-VI genotypes, with a variation of 73.3%. Overall, our findings show a relationship between the taste papillae environment and the CA-VI genetic mutation at rs2274333, which influenced the gustatory preference for dietary fat and bitter taste.

VirtuousPocketome: a computational tool for screening protein-ligand complexes to identify similar binding sites.

Protein residues within binding pockets play a critical role in determining the range of ligands that can interact with a protein, influencing its structure and function. Identifying structural similarities in proteins offers valuable insights into their function and activation mechanisms, aiding in predicting protein-ligand interactions, anticipating off-target effects, and facilitating the development of therapeutic agents. Numerous computational methods assessing global or local similarity in protein cavities have emerged, but their utilization is impeded by complexity, impractical automation for amino acid pattern searches, and an inability to evaluate the dynamics of scrutinized protein-ligand systems. Here, we present a general, automatic and unbiased computational pipeline, named VirtuousPocketome, aimed at screening huge databases of proteins for similar binding pockets starting from an interested protein-ligand complex. We demonstrate the pipeline's potential by exploring a recently-solved human bitter taste receptor, i.e. the TAS2R46, complexed with strychnine. We pinpointed 145 proteins sharing similar binding sites compared to the analysed bitter taste receptor and the enrichment analysis highlighted the related biological processes, molecular functions and cellular components. This work represents the foundation for future studies aimed at understanding the effective role of tastants outside the gustatory system: this could pave the way towards the rationalization of the diet as a supplement to standard pharmacological treatments and the design of novel tastants-inspired compounds to target other proteins involved in specific diseases or disorders. The proposed pipeline is publicly accessible, can be applied to any protein-ligand complex, and could be expanded to screen any database of protein structures.

Neuroscience of taste: unlocking the human taste code.

Since antiquity human taste has been divided into 4-5 taste qualities. We realized in the early 1970s that taste qualities vary between species and that the sense of taste in species closer to humans such as primates should show a higher fidelity to human taste qualities than non-primates (Brouwer et al. in J Physiol 337:240, 1983). Here we present summary results of behavioral and single taste fiber recordings from the distant South American marmoset, through the Old World rhesus monkey to chimpanzee, the phylogenetically closest species to humans. Our data show that in these species taste is transmitted in labelled-lines to the CNS, so that when receptors on taste bud cells are stimulated, the cell sends action potentials through single taste nerve fibers to the CNS where they create taste, whose quality depends on the cortical area stimulated. In human, the taste qualites include, but are perhaps not limited to sweet, sour, salty, bitter and umami. Stimulation of cortical taste areas combined with inputs from internal organs, olfaction, vision, memory etc. leads to a choice to accept or reject intake of a compound. The labelled-line organization of taste is another example of Müller's law of specific nerve energy, joining other somatic senses such as vision (Sperry in J Neurophysiol 8:15-28, 1945), olfaction (Ngai et al. in Cell 72:657-666, 1993), touch, temperature and pain to mention a few.

A quantitative study of the development of taste pores in mice.

OBJECTIVES: This study determined the early development of taste buds by observing the changes in the three-dimensional structures of taste pores and microvilli in the circumvallate papillae (CVP) of mice, from pre- and postnatal stages to the adult stages. METHODS: Fragments of mouse CVP tissue were collected on embryonic day (E) 18 and postnatal days (P) 0, 3, 6, 7, 14, 21, 28, and 56. The surfaces of the tissue fragments located pore apertures via scanning electron microscopy, and the sizes of the CVP and maximum diameters of the pores were estimated from the recorded images. Likewise, changes in the structures of the epithelium around the pore aperture and microvilli protruding from the pores were examined. RESULTS: The size of the CVP exhibited a linear increase with age from E18 to P56. The epithelium around the pore aperture demonstrated changes to form microridges, indicating a characteristic pattern during CVP development. The size of the pore aperture also increased with age from E18 to P56. Furthermore, an increase in the number of pores with protruding microvilli was observed at the base of the epithelial trench. A significant positive correlation was observed between the maximum diameter of the pore and the size of the CVP. CONCLUSIONS: The expansion in the lateral view of the CVP was associated with the developmental stage from E18 to P56, suggesting that the growth of the CVP leads to the opening and enlargement of the taste pores with microvillus projections during these stages.

Cyclophosphamide induces the loss of taste bud innervation in mice.

Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taste receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers that innervate them. Here, we evaluate cyclophosphamide's effects on the peripheral gustatory nerve fibers that innervate the taste buds. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallates taste buds within 4 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to visualize the peripheral gustatory nerve fibers within individual fungiform taste buds up to 20 days after CYP treatment. We find that gustatory fibers retract from the taste bud properly but are maintained within the central papilla core. These data indicate that in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss.

Bitter taste receptors in the reproductive system: Function and therapeutic implications.

Type 2 taste receptors (TAS2Rs), traditionally known for their role in bitter taste perception, are present in diverse reproductive tissues of both sexes. This review explores our current understanding of TAS2R functions with a particular focus on reproductive health. In males, TAS2Rs are believed to play potential roles in processes such as sperm chemotaxis and male fertility. Genetic insights from mouse models and human polymorphism studies provide some evidence for their contribution to male infertility. In female reproduction, it is speculated that TAS2Rs influence the ovarian milieu, shaping the functions of granulosa and cumulus cells and their interactions with oocytes. In the uterus, TAS2Rs contribute to uterine relaxation and hold potential as therapeutic targets for preventing preterm birth. In the placenta, they are proposed to function as vigilant sentinels, responding to infection and potentially modulating mechanisms of fetal protection. In the cervix and vagina, their analogous functions to those in other extraoral tissues suggest a potential role in infection defense. In addition, TAS2Rs exhibit altered expression patterns that profoundly affect cancer cell proliferation and apoptosis in reproductive cancers. Notably, TAS2R agonists show promise in inducing apoptosis and overcoming chemoresistance in these malignancies. Despite these advances, challenges remain, including a lack of genetic and functional studies. The application of techniques such as single-cell RNA sequencing and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated endonuclease 9 gene editing could provide deeper insights into TAS2Rs in reproduction, paving the way for novel therapeutic strategies for reproductive disorders.

Comparative histological and ultrastructural features of the tongue of the mallard domestic duck, Anas platyrhynchos f. domestica, Anatidae (Linnaeus, 1758) in different two age stages (post-hatching [P2] and adult female) captured from Egypt.

The domestic duck is classified as a specialist filter-feeder bird living in the water. These birds also use grazing and pecking as terrestrial feeding methods. The tongues of domestic ducks, similar to those of other Anseriformes, exhibit numerous types and shapes of mechanical papillae that serve a number of purposes when collecting food. The current study attempts to describe the morphological characteristics of the tongue as well as the mechanical papillae's development. In addition, the study aims to determine whether the papillae observed post-hatching (P2) exhibit similar morphology to those found in adult female avian species, as well as to investigate the readiness of the tongue to fulfill its feeding function following hatching. The comprehensive examination of lingual mucosa is examined about the structural modifications necessary for this variety of feeding activities. In this study, the tongues of nine young (P2) and adult female were used. The tongue had three distinct parts: the apex, which had a lingual nail on its ventral surface; the body, which exhibits numerous small and large conical papillae on its lateral sides and a lingual prominence in the caudal region; and the root, which is covered with numerous conical papillae of varying sizes. Conical, filiform, and hair-like mechanical papillae, the three types of food filtration apparatus, are present in both stages. The intraoral transfer involves several structures, including the median groove, lingual combs, and the rostral border of the lingual prominence. The rostral border of the lingual prominence is characterized by distinct rows of conical papillae. The histological analysis demonstrated the presence of both keratinized and nonkeratinized epithelium on different tongue regions. The lingual salivary glands in the rostral and caudal lingual salivary glands exhibit a pronounced periodic acid-Schiff-positive reaction. Additionally, the yellow adipose tissue and sensory receptors, namely the Grandry and Herbst corpuscles, which collectively form the bill-tongue organ that monitors the movement of food. These results conclude the presence of microstructural species-specific alterations in specific tongue areas of domestic ducks' lingual mucosa. These modifications are formed by the filtering mechanism and terrestrial feeding mechanisms, such as grazing or pecking. Following hatching, the tongue of the domestic duck undergoes significant development, primarily in preparation for grazing activities. The anatomical and histological structure of the young (P2) tongue exhibited similarities to that of the adult female domestic duck while also displaying certain variations that could potentially be attributed to the bird's habitat and mode of feeding. RESEARCH HIGHLIGHTS: The results of this study concluded that the domestic duck exhibit a complex tongue structure characterized by the arrangement and morphology of its mechanical papillae, the presence of the lingual prominence with distinctive shape and the lingual comb. These features are believed to be adaptations that enable the duck to actively and efficiently filter food particles from water, serving as its primary feeding mechanism. Additionally, the tongue of domestic ducks is specifically adapted to facilitate various terrestrial activities, such as grazing and pecking. This adaptation is achieved through the presence of conical papillae and a lingual nail. These investigations facilitate our comprehension of both the anatomical and histological characteristics of the domestic duck tongue, as well as enhance our understanding of bird adaptations to various feeding mechanisms.

Putative role of endothelin receptor B in the development and maintenance of taste buds within the circumvallate papillae.

This study aimed to achieve a better understanding of taste receptor cell development relative to endothelin receptor B (ETB) in circumvallate papillae (CVP). ETB localization was assessed by immunohistochemistry during tongue development of the mouse. Co-localization of ETB with taste receptor type III cell marker, Synaptosomal-Associated Protein 25 kDa (SNAP25), was evident in both the developing and adult CVP. ETB was strongly localized in the stromal core region. As development progressed, ETB became localized in the CVP mesenchyme and partially in the epithelium. ETB and SNAP25 co-localization indicates that ETB may regulate innervation from the CVP mesenchyme to taste buds.

A novel biomimetic electrochemical taste-biosensor based on conformational changes of the taste receptor.

Taste sensor, a useful tool which could detect and identify thousands of different chemical substances in liquid environments, has attracted continuous concern from beverage and foodstuff industry and its consumers. Although many taste sensing methods have been extensively developed, the assessment of tastant content remains challenging due to the limitations of sensor selectivity and sensitivity. Here we present a novel biomimetic electrochemical taste-biosensor based on bioactive sensing elements and immune amplification with nanomaterials carrier to address above concerns, while taking sweet taste perception as a model. The proposed biosensor based on ligand binding domain (T1R2 VFT) of human sweet taste receptor protein showed human mimicking character and initiated the application of immune recognition in gustation biosensor, which can precisely and sensitively distinguish sweet substances against other related gustation substances with detection limit of 5.1 pM, far less than that of taste sensors without immune amplification whose detection limit was 0.48 nM. The performance test demonstrated the biosensor has the capacity of monitoring the response of sweet substances in real food environments, which is crucial in practical. This biomimetic electrochemical taste-biosensor can work as a new screening platform for newly developed tastants and disclose sweet perception mechanism.

The effect of bariatric surgery on the expression of gastrointestinal taste receptors: A systematic review.

Gastrointestinal nutrient sensing via taste receptors may contribute to weight loss, metabolic improvements, and a reduced preference for sweet and fatty foods following bariatric surgery. This review aimed to investigate the effect of bariatric surgery on the expression of oral and post-oral gastrointestinal taste receptors and associations between taste receptor alterations and clinical outcomes of bariatric surgery. A systematic review was conducted to capture data from both human and animal studies on changes in the expression of taste receptors in oral or post-oral gastrointestinal tissue following any type of bariatric surgery. Databases searched included Medline, Embase, Emcare, APA PsychInfo, Cochrane Library, and CINAHL. Two human and 21 animal studies were included. Bariatric surgery alters the quantity of many sweet, umami, and fatty acid taste receptors in the gastrointestinal tract. Changes to the expression of sweet and amino acid receptors occur most often in intestinal segments surgically repositioned more proximally, such as the alimentary limb after gastric bypass. Conversely, changes to fatty acid receptors were observed more frequently in the colon than in the small intestine. Significant heterogeneity in the methodology of included studies limited conclusions regarding the direction of change in taste receptor expression induced by bariatric surgeries. Few studies have investigated associations between taste receptor expression and clinical outcomes of bariatric surgery. As such, future studies should look to investigate the relationship between bariatric surgery-induced changes to gut taste receptor expression and function and the impact of surgery on taste preferences, food palatability, and eating behaviour.Registration code in PROSPERO: CRD42022313992.

Tongue microarchitecture and functional characterization of the lingual papillae in the desert hedgehog (Paraechinus aethiopicus).

The present work attempted to provide a comprehensive description of the morphoanatomical, histological, and ultrastructural characteristics of the tongue in the desert hedgehog (Paraechinus aethiopicus), and to correlate lingual modifications to the feeding lifestyle. Five adult male hedgehogs were utilized in our investigation. The macroscopic observations revealed elongated, with a moderately pointed apex, tongue and the tongue dorsum lacks both lingual prominence and median sulcus. The main subdivisions of the tongue are radix linguae (root), corpus linguae (body), and apex linguae (apex). The tongue dorsum carries two types of mechanical (conical and filiform) and gustatory (fungiform and circumvallate) papillae. The lingual apex is characterized by the existence of a unique encapsulated muscular structure. Additionally, the lingual glands were interposed between the muscular strands and no lingual glands were detected on the lingual apex. The dorsal surface of the lingual apex exhibited the highest level of keratinization as revealed by histochemical staining while the root showed moderate staining. The topography of the tongue was investigated by scanning electron microscopy (SEM). The obtained results are important to provide basic knowledge that can contribute to better understanding of the nourishment, feeding habits and behavior in this species. Furthermore, the addition of the newly investigated species may help us to determine the evolutionary relationships among species.

Standing gustatory papillae biopsy procedure for antemortem diagnosis of equine grass sickness.

OBJECTIVE: Diagnosing equine grass sickness (EGS) requires histopathological evidence of chromatolysis and/or neuronal loss in peripheral autonomic ganglia. Previous investigators performed postmortem biopsies of gustatory papillae located on the tongue and found chromatolytic subgemmal neurons in all 13 EGS horses. The present study aimed to design a standardized lingual biopsy sampling method through a transbuccal approach in healthy standing horses and assess the quality of the obtained samples, to allow antemortem diagnosis of EGS in clinical cases. ANIMALS: 6 healthy horses. METHODS: A transbuccal approach was performed bilaterally in 6 healthy standing horses. After having reached a deep level of sedation, horses were placed in stocks and a Günther mouth gag was inserted. Local anesthesia followed by a vertical full thickness incision was performed on both cheeks. Foliate papillae biopsies were carried out using an arthroscopic rongeur inserted through each incision site under oral endoscopic control. Tongue movements were restricted with diazepam. Histological assessment of taste buds and subgemmal plexi neurons was performed using H&E-stained longitudinal sections. RESULTS: The procedure was well tolerated in all horses. Minor complications observed were a transient facial paralysis, some incisional fluid collection, and abscesses. Ten samples (10/12) were suitable for assessment of neuronal perikarya. CLINICAL RELEVANCE: This procedure was safe for subgemmal plexus biopsy in healthy standing horses. The obtained samples were adequate as long as they were neatly cut lengthwise for inclusion. The technique was also used for 2 clinical cases and revealed the complete absence of neuronal perikarya, confirming chronic EGS.