The brain of Drosophila melanogaster is comprised of some 100,00 neurons, 127 and 80 of which are dopaminergic and serotonergic, respectively. Their activity regulates behavioral functions equivalent to those in mammals, e.g. motor activity, reward and aversion, memory formation, feeding, sexual appetite etc. Mammalian dopaminergic and serotonergic neurons are known to be heterogeneous. They differ in their projections and in their gene expression profile. A sophisticated genetic tool box is available, which allows for targeting virtually any gene with amazing precision in Drosophila melanogaster. Similarly, Drosophila genes can be replaced by their human orthologs including disease-associated alleles. Finally, genetic manipulation can be restricted to single fly neurons. This has allowed for addressing the role of individual neurons in circuits, which determine attraction and aversion, sleep and arousal, odor preference etc. Flies harboring mutated human orthologs provide models, which can be interrogated to understand the effect of the mutant protein on cell fate and neuronal connectivity. These models are also useful for proof-of-concept studies to examine the corrective action of therapeutic strategies. Finally, experiments in Drosophila can be readily scaled up to an extent, which allows for drug screening with reasonably high throughput.

A growing body of research aims at solving what is often referred to as the stimulus-percept problem in olfactory perception. Although computational efforts have made it possible to predict perceptual impressions from the physicochemical space of odors, studies with large psychophysical data sets from non-experts remain scarce. Following previous approaches, we developed a physicochemical odor space using 4,094 molecular descriptors of 1,389 odor molecules. For 20 of these odors, we examined associations with perceived pleasantness, intensity, odor quality and detection threshold, obtained from a dataset of 2,000 naïve participants. Our results show significant differences in perceptual ratings, and we were able to replicate previous findings on the association between perceptual ratings and the first dimensions of the physicochemical odor space. However, the present analyses also revealed striking interindividual variations in perceived pleasantness and intensity. Additionally, interactions between pleasantness, intensity, and olfactory and trigeminal qualitative dimensions were found. Our results support previous findings on the relation between structure and perception on the group level in our sample of non-expert raters. Nevertheless, human olfactory perception is no analytic process of molecule detection alone. Therefore, to gain an understanding of stimulus-percept relationship in the individual, future studies should shift towards a more holistic view that takes into account the influences of context, experience and other interpersonal characteristics.

In healthy humans, taste sensitivity varies widely, influencing food selection and nutritional status. Chemosensory reductions have been associated with numerous pathological disorders or pharmacological interventions. Reliable psychophysical methods are crucial resources to analyze the taste function during routine clinical assessment. However, in the daily clinical routine, they are often considered to be too time-consuming. We used the Supervised Learning (SL) regression method to analyze with high precision the overall taste status of healthy controls (HC) and patients with chemosensory loss and to characterize the combination of responses that best can predict the overall taste status of two groups. Random Forest regressor allowed us to achieve our objective. The analysis of the order of importance and impact of each parameter on the prediction of overall taste status 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. The identification of these distinctions appears to be of interest to the health system since they may allow the use of specific stimuli during routine clinical assessments of taste function reducing the commitment in terms of time and costs.

Taste disorders are common among cancer patients undergoing chemotherapy, with a prevalence ranging from 20% to 86%, persisting throughout treatment. This condition leads to reduced food consumption, increasing the risk of malnutrition. Malnutrition is associated not only with worse treatment efficacy and poor disease prognosis but also with reduced functional status and quality of life. The fruit of Synsepalum dulcificum (Daniell), commonly known as miracle berry or miracle fruit, contains miraculin, a taste-modifying protein with profound effects on taste perception. The CLINMIR Protocol is a triple-blind, randomized, placebo-controlled clinical trial designed to evaluate the regular consumption of a food supplement containing a miraculin-based novel food, dried miracle berry (DMB), on the taste perception (measured through electrogustometry) and nutritional status (evaluated through the GLIM Criteria) of malnourished cancer patients under active antineoplastic treatment. To this end, a pilot study was designed with 30 randomized patients divided into three study arms (150 mg DMB + 150 mg freeze-dried strawberries, 300 mg DMB or placebo) for three months. Throughout the five main visits, an exhaustive assessment of different affected parameters susceptible to improvement through regular consumption of the miraculin-based food supplement will be conducted, including electrical and chemical taste perception, smell perception, nutritional and morphofunctional assessment, diet, quality of life, fatty acid profile of erythrocytes, levels of inflammatory and cancer-associated cytokines, oxidative stress, antioxidant defense system, plasma metabolomics, and saliva and stool microbiota. The primary anticipated result is that malnourished cancer patients with taste distortion who consume the miraculin-based food supplement will report an improvement in food taste perception. This improvement translates into increased food intake, thereby ameliorating their nutritional status and mitigating associated risks. Additionally, the study aims to pinpoint the optimal dosage that provides maximal benefits. The protocol adheres to the SPIRIT 2013 Statement, which provides evidence-based recommendations and is widely endorsed as an international standard for trial protocols (https://www.spirit-statement.org/spirit-statement/). The clinical trial protocol has been registered at http://clinicaltrials.gov (NCT05486260).