The sense of taste: Development, regeneration, and dysfunction.

Gustation or the sense of taste is a primary sense, which functions as a gatekeeper for substances that enter the body. Animals, including humans, ingest foods that contain appetitive taste stimuli, including those that have sweet, moderately salty and umami (glutamate) components, and tend to avoid bitter-tasting items, as many bitter compounds are toxic. Taste is mediated by clusters of heterogeneous taste receptors cells (TRCs) organized as taste buds on the tongue, and these convey taste information from the oral cavity to higher order brain centers via the gustatory sensory neurons of the seventh and ninth cranial ganglia. One remarkable aspect of taste is that taste perception is mostly uninterrupted throughout life yet TRCs within buds are constantly renewed; every 1-2 months all taste cells have been steadily replaced. In the past decades we have learned a substantial amount about the cellular and molecular regulation of taste bud cell renewal, and how taste buds are initially established during embryogenesis. Here I review more recent findings pertaining to taste development and regeneration, as well as discuss potential mechanisms underlying taste dysfunction that often occurs with disease or its treatment. This article is categorized under: Infectious Diseases > Stem Cells and Development Cancer > Stem Cells and Development Neurological Diseases > Stem Cells and Development.

The impact of injury of the chorda tympani nerve during primary stapes surgery or cochlear implantation on taste function, quality of life and food preferences: A study protocol for a double-blind prospective prognostic association study.

BACKGROUND: The chorda tympani nerve (CTN) is a mixed nerve, which carries sensory and parasympathetic fibres. The sensory component supplies the taste sensation of the anterior two-thirds of the ipsilateral side of the tongue. During middle ear surgery the CTN is exposed and frequently stretched or sacrificed, because it lacks a bony covering as it passes through the middle ear. Injury may cause hypogeusia, ageusia or altered taste sensation of the ipsilateral side of the tongue. To date, there is no consensus regarding which type of CTN injury (sacrificing or stretching), during middle ear surgery, leads to the least burden for the patient. METHODS: A double-blind prospective prognostic association study was designed in a single medical centre in the Netherlands to determine the effect of CTN injury on postoperative taste disturbance and quality of life. 154 patients, who will undergo primary stapes surgery or cochlear implantation will be included. The taste sensation, food preferences and quality of life of these patients will be evaluated preoperatively and at one week, six weeks and six months postoperatively using the Taste Strip Test, Electrogustometry, supplementary questionnaire on taste disturbance, Macronutrient and Taste Preference Ranking Task, Appetite, Hunger and Sensory Perception questionnaire and Questionnaire of Olfactory Disorders to assess the association of these outcomes with CTN injury. Evaluation of olfactory function will only take place preoperatively and at one week postoperatively using the Sniffin' Sticks. The patient and outcome assessor are blinded to the presence or absence of CTN injury. DISCUSSION: This study is the first to validate and quantify the effect of chorda tympani nerve injury on taste function. The findings of this study may lead to evidence-based proof of the effect of chorda tympani injury on taste function with consequences for surgical strategies. TRIAL REGISTRATION: Netherlands Trial Register NL9791. Registered on 10 October 2021.

Antibody response, associated symptoms and profile of patients presumably infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study.

BACKGROUND: Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders. METHODS: We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. RESULTS: The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. CONCLUSIONS: Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

[Mechanisms and Management of COVID-19-Associated Taste Disorders].

The taste buds in the human tongue contain specialized cells that generate taste signals when they are stimulated. These signals are then transmitted to the central nervous system, allowing the human body to distinguish nutritious substances from toxic or harmful ones. This process is critical to the survival of humans and other mammals. A number of studies have shown that dysgeusia, or taste disorder, is a common complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can severely affect patients' nutritional intake and quality of life. Based on the physiological process of taste perception, the direct causes of dysgeusia include dysfunction of taste receptors and damage to the taste nervous system, while indirect causes include genetic factors, aging-related changes, bacterial and viral infections, and cancer treatments such as radiotherapy and chemotherapy. The pathogenic factors of dysgeusia are complicated, further research is needed to fully understand the underlying mechanisms, and some of the reported findings and conclusions still need further validation. All these form a great challenge for clinical diagnosis of the cause and targeted treatment of dysgeusia. Herein, we reviewed published research on the physiological process of taste perception, the potential mechanisms of taste disorders related to SARS-CoV-2 infection, and strategies for prevention and treatment, providing theoretical support for establishing and improving the comprehensive management of COVID-19 complicated by taste disorders.

A systematic review of the biological mediators of fat taste and smell.

Taste and smell play a key role in our ability to perceive foods. Overconsumption of highly palatable energy-dense foods can lead to increased caloric intake and obesity. Thus there is growing interest in the study of the biological mediators of fat taste and associated olfaction as potential targets for pharmacologic and nutritional interventions in the context of obesity and health. The number of studies examining mechanisms underlying fat taste and smell has grown rapidly in the last 5 years. Therefore, the purpose of this systematic review is to summarize emerging evidence examining the biological mechanisms of fat taste and smell. A literature search was conducted of studies published in English between 2014 and 2021 in adult humans and animal models. Database searches were conducted using PubMed, EMBASE, Scopus, and Web of Science for key terms including fat/lipid, taste, and olfaction. Initially, 4,062 articles were identified through database searches, and a total of 84 relevant articles met inclusion and exclusion criteria and are included in this review. Existing literature suggests that there are several proteins integral to fat chemosensation, including cluster of differentiation 36 (CD36) and G protein-coupled receptor 120 (GPR120). This systematic review will discuss these proteins and the signal transduction pathways involved in fat detection. We also review neural circuits, key brain regions, ingestive cues, postingestive signals, and genetic polymorphism that play a role in fat perception and consumption. Finally, we discuss the role of fat taste and smell in the context of eating behavior and obesity.

Alterations in smell or taste in individuals infected with SARS-CoV-2 during periods of Omicron variant dominance.

OBJECTIVES: To characterize the prevalence, severity, correlation with initial symptoms, and role of vaccination in patients with COVID-19 with smell or taste alterations (STAs). METHODS: We conducted an observational study of patients infected with SARS-CoV-2 Omicron admitted to three hospitals between May 17 and June 16, 2022. The olfactory and gustatory functions were evaluated using the taste and smell survey and the numerical visual analog scale at two time points. RESULTS: The T1 and T2 time point assessments were completed by 688 and 385 participants, respectively. The prevalence of STAs at two time points was 41.3% vs 42.6%. Furthermore, no difference existed in the severity distribution of taste and smell survey, smell, or taste visual analog scale scores between the groups. Patients with initial symptoms of headache (P = 0.03) and muscle pain (P = 0.04) were more likely to develop STAs, whereas higher education; three-dose vaccination; no symptoms yet; or initial symptoms of cough, throat discomfort, and fever demonstrated protective effects, and the results were statistically significant. CONCLUSION: The prevalence of STAs did not decrease significantly during the Omicron dominance, but the severity was reduced, and vaccination demonstrated a protective effect. In addition, the findings suggest that the presence of STAs is likely to be an important indicator of viral invasion of the nervous system.

Eating Habits and Body Weight Changes Induced by Variation in Smell and Taste in Patients with Previous SARS-CoV-2 Infection.

Olfactory and gustatory dysfunction are recognized as common symptoms in patients with COVID-19, with a prevalence ranging, respectively, between 41-61% and 38.2-49%. This review focused on relating the variations in dietary habits with the reduction/loss of smell and/or taste in patients who contracted the COVID-19 infection. Primarily, we reviewed the main pathological mechanisms involved in COVID 19-induced anosmia/dysosmia and ageusia/dysgeusia. Then, we explored and summarized the behavioural changes in food intake and body weight during the COVID-19 pandemic in relation to sensory impairment and the underlying mechanisms. Most studies on this topic argue that the altered chemosensory perception (taste and smell) mainly induces reduced appetite, leading to a faster fullness sensation during the consumption of a meal and, therefore, to a decrease in body weight. On the other hand, a reduced perception of the food's sensory properties may trigger compensatory responses that lead some individuals to increase food intake with a different effect on body weight. Regarding body weight, most studies evaluated malnutrition in patients hospitalized for COVID-19; more studies are warranted to investigate nutritional status specifically in non-hospitalized patients with olfactory and gustatory dysfunctions caused by COVID-19 infection.

Role of Aromatic Herbs and Spices in Salty Perception of Patients with Hyposmia.

Herbs and spices represent a possibility for the improvement of anosmia and ageusia. In this work we evaluated the role of Mediterranean aromatic herbs and spices in the salty taste perception of patients with hyposmia compared to healthy controls. To this goal, the salty taste perception in response to pure salt and different types of commercial flavored sea salt was assessed in patients with hyposmia, with or without a post-acute coronavirus syndrome, and healthy controls. Myrtle berries and leaves, a mixture of Mediterranean herbs and plants such as helichrysum, rosemary, liquorice, fennel seeds and myrtle leaves, oranges and saffron were used as salt flavoring ingredients. Differences in gustatory perception between 57 patients with hyposmia and 91 controls were evaluated considering the rate of the gustatory dimensions of pleasantness, intensity, and familiarity, using a 7-point hedonic Likert-type scale. At a dose of 0.04 g/mL, saline solutions of flavored salts, with an average 15% less NaCl, were perceived by patients with hyposmia as equally intense but less familiar than pure salt solution, with similar scores in the pleasantness dimension. Our study highlighted the central role of Mediterranean aromatic plants in the enhancement of salty perception in patients with hyposmia.

[Functional and morphological disorders of taste and olfaction in COVID-19 patients]. / Funktionelle und morphologische Geschmacks- und Geruchsstörungen bei COVID-19-Patienten.

OBJECTIVE: This study aimed to test the prevalence and evolution of acute olfactory and gustatory functional impairment and their morphologic correlates in COVID-19 patients who require hospitalization due to COVID-19-related respiratory conditions. METHODS: Included were 53 consecutive hospitalized patients (23 males, 30 females; age 42.54 ± 10.95 years) with an RT-PCR-confirmed COVID-19 diagnosis. Patients were examined twice: just after hospital discharge and 4-6 weeks later. Electrogustometric (EGM) thresholds at the tongue area supplied by the chorda tympani, at the soft palate, and in the region of the vallate papillae were recorded bilaterally. Olfaction was examined by Sniffin' sticks (Burghardt GmbH, Wedel, Germany). The patients' nasal and oral mucosa (fungiform papillae, fpap) were examined by contact endoscopy. Findings were compared to those of 53 healthy individuals matched for sex and age (23 males, 30 females; age 42.90 ± 10.64 years). RESULTS: EGM thresholds in patients were significantly higher than those of healthy subjects at both timepoints. EGM thresholds at the second measurement were significantly lower than those at the first measurement. Accordingly, patient-reported gustatory outcomes were improved at the second measurement. The same pattern was found using Sniffin' sticks. Significant alterations in form and vascularization of fPap were detected in patients, especially at the first instance. Interestingly we did not observe any significant changes in the morphology and vascularization of nasal mucosa. CONCLUSION: COVID-19 affects both gustatory and olfactory functions. In parallel, it also affects the structure and vascularization of both nasal and oral mucosa, albeit the nasal mucosa to a much lesser, non-significant extent. Our findings suggest that COVID-19 may cause a mild to profound neuropathy of multiple cranial nerves.

Tongue immune compartment analysis reveals spatial macrophage heterogeneity.

The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication, and articulation. As a barrier organ, which is constantly exposed to environmental pathogens, the tongue is expected to host an immune cell network ensuring local immune defence. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here, we characterised the tissue-resident immune compartment of the murine tongue during development, health and disease, combining single-cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1+ macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae. Folr2+ macrophages were detected in deeper muscular tissue. In silico analysis indicated that the two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPS in vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders.

Not Only COVID-19: Involvement of Multiple Chemosensory Systems in Human Diseases.

Chemosensory systems are deemed marginal in human pathology. In appraising their role, we aim at suggesting a paradigm shift based on the available clinical and experimental data that will be discussed. Taste and olfaction are polymodal sensory systems, providing inputs to many brain structures that regulate crucial visceral functions, including metabolism but also endocrine, cardiovascular, respiratory, and immune systems. Moreover, other visceral chemosensory systems monitor different essential chemical parameters of "milieu intérieur," transmitting their data to the brain areas receiving taste and olfactory inputs; hence, they participate in regulating the same vital functions. These chemosensory cells share many molecular features with olfactory or taste receptor cells, thus they may be affected by the same pathological events. In most COVID-19 patients, taste and olfaction are disturbed. This may represent only a small portion of a broadly diffuse chemosensory incapacitation. Indeed, many COVID-19 peculiar symptoms may be explained by the impairment of visceral chemosensory systems, for example, silent hypoxia, diarrhea, and the "cytokine storm". Dysregulation of chemosensory systems may underlie the much higher mortality rate of COVID-19 Acute Respiratory Distress Syndrome (ARDS) compared to ARDSs of different origins. In chronic non-infectious diseases like hypertension, diabetes, or cancer, the impairment of taste and/or olfaction has been consistently reported. This may signal diffuse chemosensory failure, possibly worsening the prognosis of these patients. Incapacitation of one or few chemosensory systems has negligible effects on survival under ordinary life conditions but, under stress, like metabolic imbalance or COVID-19 pneumonia, the impairment of multiple chemosensory systems may lead to dire consequences during the course of the disease.

Evaluation of Acoustic Reflex Thresholds in COVID-19 Patients With Taste Disorders.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can result in persistent loss of taste and smell. This study was performed to assess acoustic reflex threshold (ART) in patients with taste disorders caused by SARS-CoV-2. MATERIAL AND METHODS: This retrospective study enrolled 11 patients (9 men, 2 women; average age = 22.3 years) with a history of COVID-19 and had complaints of taste disorder and sensitivity to loud sounds. The control group consisted of 13 healthy participants (10 men, 3 women; average age = 23.4 years). Anamnesis, neuro-otological, ear, nose and throat, and eye examinations, as well as a taste test, pure tone audiometry, speech discrimination test, and impedance audiometry were performed in all participants. RESULTS: All participants in the study group had a negative taste test result. In addition, ART values were significantly higher in the study group than the control group at all frequencies. CONCLUSIONS: SARS-CoV-2 could be a neurotropic virus that can cause facial nerve neuropathy.

Assessment of Taste Function.

Taste disorders, impacting well-being and physical health, can be caused by many etiologies including the use of medication. Recently, taste disturbance is also considered as one of the predominant symptoms of COVID-19 although its pathogenesis requires further research. Localized taste disorders may be overlooked considering that whole-mouth taste perception is insured through several mechanisms. Individuals often fail to discern taste from flavor, and interviews/surveys are insufficient to properly assess taste function. Hence, various taste assessment methods have been developed. Among them, psychophysical methods are most widely applied in a clinical context. Less-biased electrophysiological, imaging, or morphological methods are used to a much lesser degree. Overall, more research is needed in the field of taste.

Characteristics of COVID-19 smell and taste dysfunction in hospitalized patients.

The effects of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist on a spectrum. Clinical symptoms of smell and taste dysfunction are prominent features of COVID-19. The objective of this study was to elucidate the factors associated with smell and taste dysfunction amongst hospitalized COVID-19 patients. A retrospective review of a multi-hospital health network's COVID-19 database between March and June 2020 was performed. Patients with self-reported smell or taste loss were included. Demographic information, patient comorbidities, and mortality data was obtained. There were 2892 patients included in this analysis and 117 reported smell or taste loss (4.0%, 95% confidence interval [CI]: 3.4%-4.8%). The proportion of females with smell or taste loss was significantly higher than males (6.3% vs. 2.5%, P < 0.001), whereas no differences existed between ethnicity or smoking status. When compared with age of 30-40 years, the age group of 10-20 years were most likely to present with smell or taste dysfunction (odds ratio [OR] 6.59, 95% CI 1.32-26.12; P = 0.01). The majority of specific comorbidities were not associated with increased incidence of smell or taste dysfunction. Outpatient healthcare workers were more likely to present with smell or taste loss (OR 3.2, CI 1.8-5.47; P < 0.001). The mortality rate among COVID-19 patients with smell or taste dysfunction was significantly lower than those without (0% vs. 20.3%; P < 0.001). Smell or taste loss is more prevalent in women, younger age groups, and healthier individuals. It may be associated with lower mortality and a milder disease trajectory compared to the overall cohort.

Six-month smell and taste recovery rates in coronavirus disease 2019 patients: a prospective psychophysical study.

BACKGROUND: The long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified. METHODS: Olfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation. RESULTS: A total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent. CONCLUSION: Six months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.

Smell and taste disorders in COVID-19: From pathogenesis to clinical features and outcomes.

Patients with COVID-19 often complain of smell and taste disorders (STD). STD emerge early in the course of the disease, seem to be more common in SARS-CoV-2 infection than in other upper respiratory tract infections, and could in some cases persist for long after resolution of respiratory symptoms. Current evidence suggests that STD probably result from a loss of function of olfactory sensory neurons and taste buds, mainly caused by infection, inflammation, and subsequent dysfunction of supporting non-neuronal cells in the mucosa. However, the possible occurrence of other mechanisms leading to chemosensory dysfunction has also been hypothesized, and contrasting data have been reported regarding the direct infection of sensory neurons by SARS-CoV-2. In this mini-review, we summarize the currently available literature on pathogenesis, clinical manifestations, diagnosis, and outcomes of STD in COVID-19 and discuss possible future directions of research on this topic.

Pathogenesis of dysgeusia in COVID-19 patients: a scoping review.

OBJECTIVE: The novel coronavirus disease-19 (COVID-19) pandemic had intense social and economic effects. Patients infected with COVID-19 may present with a series of conditions. A considerable number of patients express taste and smell disturbances as a prodromal, coexistent, or as the only manifestation of COVID-19 infection. The objective of the present review is to review the hypothetical mechanisms of action and etiopathogenesis of dysgeusia in COVID-19 patients. MATERIALS AND METHODS: Multiple scientific databases were explored, including PubMed, Medline, Scopus, Cochrane-library, LILACS, Livivo and OpenGrey. All types of articles that discussed the pathogenesis of dysgeusia were included, while articles that described dysgeusia without detail about its mode of action were excluded. RESULTS: A total of 47 articles, with different designs, were included in this review. These articles suggested direct viral neural invasion to olfactory and gustatory nerves, viral cytotoxicity to taste buds, angiotensin II imbalance, augmented pro-inflammatory cytokines, and disturbances in salivary glands and sialic acid. COVID-19 induced-dysgeusia was also associated with systemic diseases, medications, zinc, chemicals, and disinfectants. CONCLUSIONS: The most likely cause of transient dysgeusia in COVID-19 is peripheral neurotropism and direct toxicity to taste buds or olfactory epithelium. Other factors may also play a contributory role in dysgeusia, such as a defect in the quality and quantity of saliva, pro-inflammatory cytokines, angiotensin II accumulation, systemic diseases, hypozincemia, and excessive use of chemicals.

Smell and taste loss in COVID-19 patients: assessment outcomes in a Victorian population.

Background: It has been noted that olfactory and gustatory disturbances may precede or accompany the typical features of COVID-19, such as fever and cough. Hence, a high index of suspicion is required when patients report sudden loss of smell or taste, in order to facilitate timely diagnosis and isolation.Aims/objectives: The aim of this study was to assess the frequency of olfactory and gustatory disturbances in COVID-19 positive patients from a cohort representative of Melbourne, Australia.Methods: A retrospective descriptive study was conducted on patients who tested positive for COVID-19. Standardised phone consultations and online follow-up questionnaires were performed to assess clinical features of COVID-19, with a focus on smell and taste disorders.Results: The most frequent symptoms experienced were taste and smell disturbances with 74% experiencing either smell or taste disturbance or both. Post-recovery, 34% of patients continued to experience ongoing hyposmia and 2% anosmia, whereas 28% continued to suffer from hypogeusia or ageusia.Conclusion and significance: This study presents the high rates of improvement of both olfactory and gustatory disturbance in a short-lived period. It also highlights the importance of these symptoms in prompting appropriate testing, quarantine precautions, initiate early olfactory retraining and the potential for continued sensory disturbance.

Decrease and Recovery of Olfactory and Gustatory Function in a Case of SARS-CoV-2 Infection.

Self-reported chemosensory dysfunction in severe acute respiratory syndrome coronavirus 2 patients is common. We present a case of reversible smell loss in a young patient with mild coronavirus disease 2019 infection assessed with established testing methods over a period of 8 weeks.