Receptor Mechanisms of Cross-Modal Interaction in Odor-Induced Sweetness Enhancement (OISE): From Molecular Recognition to Health-Oriented Flavor Design

… that [he odor-induced taste enhancement did not result from the stimulation of receptors in the oral … Thus, we could show that the odor-induced taste enhancement is elicited by olfactory …

Growing demand for sugar reduction in beverage necessitates innovative approaches to maintain sweetness perception without compromising acceptability. Volatile compounds in Fu brick tea (FBT) were analyzed using headspace solid-phase microextraction (HS-SPME) combined with gas chromatography/olfactometry-associated taste (GC/O-AT), identifying four key sweetness-associated aroma compounds. Threshold determination coupled with gradient monomer recombination experiments quantified compound-specific sweetness contributions. Sensory evaluation revealed α-ionone, linalool, and sclareolide as superior enhancers, with α-ionone demonstrating optimal potency and palatability. Molecular docking simulations showed T1R2/T1R3 binding energies of -7.0 kcal/mol (sclareolide), -6.2 kcal/mol (α-ionone), -5.8 kcal/mol (geranyl isovalerate) and - 5.0 kcal/mol (linalool). However, binding energy magnitude lacked absolute correlation with sensory enhancement. Molecular dynamics simulations further confirmed stable ligand-receptor complexes mediated primarily by hydrogen bonds and hydrophobic forces. This study elucidates cross-modal aroma-taste interactions as critical drivers of sweetness perception in FBT, offering a multidisciplinary methodology to design reduced-sugar beverages with preserved sensory appeal.

… at the level of receptor cells, but … of sweetness enhancement. These findings suggest that congruency acts as a necessary condition for odor-induced taste enhancement: enhancement …

At present, there are relatively few studies on the influence of green aroma and aldehyde aroma compounds on the sweetness perception of sucrose. This study examined the effects of 11 aroma compounds from sweet orange, characterized by green and aldehyde flavors, on the sweetness of a 5 % sucrose solution. Using artificial sensory analysis and electronic tongue technology, it was found that most aromatic compounds can inhibit sweetness perception, and the inhibitory effect of trans-2-decenoaldehyde is the most significant. The mechanism of inhibition was explored through molecular simulation, revealing that the binding free energy of molecular docking was greater than −5.9 kcal/mol. Further molecular dynamics analysis showed that compared with the T1R2/T1R3 sucrose binary system, the addition of aroma substances reduced the number of hotspot residues involved in protein ligand binding, and did not enhance the binding ability of ligand proteins, indicating an inhibitory effect.

Background In the context of increasing global health risks, including obesity, diabetes, and cardiovascular diseases, odor-induced taste enhancement (OITE) has emerged as an …

… The study aimed to determine odor-induced taste enhancement (OITE) differences between … higher sweet taste enhancement than NW. We also tested salty taste enhancement without …

… effective strategies for sweetness enhancement and sugar … and molecular mechanism of sweetness perception were first … : Sweetness perception was initiated by sweet taste receptor …

… enhancing the sweet-smelling enhancing odorants by vanillin (V)/ethyl vanillin (EV)-specific receptors … Twelve odorants showed sweet-smelling enhancement ability to V and EV were …

Gas chromatography/olfactometry-associated taste (GC/O-AT) analysis combined with mass spectrometry allowed identification of odorant compounds associated with taste attributes (sweet, salty, bitter and sour) in a multi-fruit juice. Nine compounds were selected for their odor-associated sweetness enhancement in a multi-fruit juice odor context using Olfactoscan and for their odor-induced sweet taste enhancement in sucrose solution and sugar-reduced fruit juice through sensory tests. Sweetness of the fruit juice odor was significantly enhanced by methyl 2-methylbutanoate, ethyl butanoate, ethyl 2-methylbutanoate and linalool; sweet perception was significantly enhanced in 7% sucrose solution by ethyl 2-methylbutanoate, furaneol and γ-decalactone, and in 32% sugar-reduced fruit juice by ethyl 2-methylbutanoate. GC/O-AT analysis is a novel, efficient approach to select odorants associated with a given taste. The further screening of taste-associated odorants by Olfactoscan helps to identify the most efficient odorants to enhance a target taste perception and may be used to find new ways to modulate taste perception in foods and beverages.

Growing demand for sugar-reduced foods necessitates a deeper understanding of odor-induced sweetness enhancement. This study explored durian-derived volatile sulfur compounds (VSCs) as sucrose potentiators through integrated SPME-GC/MS, sensory evaluation, and computational analyses. GC/O-AT, recombination, and omission experiments identified 10 key VSCs associated with 'sweet' prioritized for investigation. Sensory evaluation identified optimal sucrose concentration (30 g/L) for sweetness amplification, particularly with S-ethyl ethanethioate and dipropyl disulfide showing significant enhancement, while dimethyl trisulfide suppressed sweetness. Molecular docking revealed stable binding of sweet-enhancing VSCs to T1R2/T1R3-sucrose complexes (-9.811 to -8.274 kcal/mol), mediated by hydrogen bonds and hydrophobic interactions in the Venus flytrap domain. Molecular dynamics confirmed that dipropyl disulfide stabilized receptor-ligand binding through multifaceted interactions. It was found that the binding energy has a certain correlation with the perceived intensity. Future research should integrate cross-modal sensory and molecular biology approaches to optimize low-sugar flavor compensation strategies.

… We found specific taste-smell interactions: sweetness enhancement induced by strawberry … and tastants, nor between odorants and taste receptors. Consequently, these results strongly …

This study explores the synergy between eight floral aroma compounds and erythritol (p < 0.05), enhancing its sweetness. While α- and β-ionone increase sweetness, they reduce overall acceptability. At optimal concentrations, these compounds improve both sweetness and flavor, but the effect diminishes beyond certain thresholds. Electronic tongue results correlate with sensory data but cannot fully replicate human taste. Molecular docking reveals ternary complexes (T1R2/T1R3-aroma-erythritol) show better binding energies than binary systems, with α-ionone having the lowest binding energy (-10.54 kcal/mol). 100-ns simulations identify ASN70, GLY381, and SER380 as key residues. Binding free energies for neryl acetate range from - 45.21 to -57.38 kcal/mol, clarifying the mechanisms of sweetness enhancement. These findings support the reduction of erythritol in juices and the development of low-sugar beverages through aroma-induced sweetness.

… However, because the enhancement effect disappeared … concluded that odor-induced taste enhancement might have … is whether odor enhancement is specific to the sweetness of …

In our previous study, phloridzin ('phl') and β-ionone ('bet') was identified as key contributors to the taste and sweet aroma of Camellia nanchuanica black tea, respectively. To study the effects of 'bet' on the sweetness of 'phl' and the specific perception mechanisms via retronasal and orthonasal pathways, we first analyzed the interactions between various concentrations of 'bet' (bet-8bet) and 'phl' (phl-8phl) using quantitative descriptive analysis. Our findings revealed that 'bet' odor significantly enhanced the sweetness of 'phl' (phl-8phl) through both retronasal and orthonasal pathways, particularly at concentrations of 2bet or greater. Subsequently, we observed that retronasal 'bet' odor sweetened 'phl' by increasing the stability between 'phl' and Taste 1 Receptor Member 3 (TAS1R3) based on determination of calcium signal and molecular dynamics simulations. However, orthonasal 'bet' odor likely heightened the perception of 'phl"s sweet taste by activating the left temporal regions of the brain, which are correlated with positive emotion.

… Yet, the most surprising aspect of this study is that an odor-induced taste enhancement … also other sources of sweet taste enhancement such as modification of receptor mechanisms. …

… and ethyl propionate) were significantly associated with sweetness, umami, and saltiness (P … the sweetness receptor T1R2/T1R3, umami receptor T1R1/T1R3, and saltiness receptor …

… sweetness of strong-aroma Baijiu is a key indicator of its widespread consumer appeal and high quality; however, the sources of its key sweet … inducing enhanced sweetness in Baijiu …

… This study focused on volatile flavor compounds found in foods and beverages that have sweet tastes and/or sweet-enhancing effects, as validated empirically. These volatile flavor …

Black tea contains sweet aroma compounds (SACs) with sweetening potential. However, a systematic understanding of their composition, enhancing effects, and underlying mechanisms is lacking. This study identified 14 key SACs in global sweet-aroma black teas using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. Electronic tongue and sensory validation confirmed their sweetness-enhancing effects in a sugar-free black tea beverage and revealed their inherent taste properties (sweetness, astringency, pungency, and cooling). Molecular docking and dynamics simulation elucidated the stable bindings of T1R2/T1R3-benzeneacetaldehyde/β-damascenone, α-amylase-benzeneacetaldehyde, TRPV1-geraniol, and TRPM8-methyl salicylate, mediated by hydrogen bonding and hydrophobic interactions. These protein-ligand complexes were proposed to modulate sweetness, sweet aftertaste, heat-evoked sweetness, and cooling-enhanced sweetness, respectively. Consequently, this study demonstrates that SACs enhance sweetness through cross-modal interactions and inherent taste properties, providing novel mechanistic insights and actionable strategies for flavor optimization in tea beverages and other food products.

Aroma-taste interactions, which are believed to occur due to previous coexposure (concurrent presence of aroma and taste), have been suggested as a strategy to aid sugar reduction in food and beverages. However, coexposures might be influenced by individual differences. We therefore hypothesized that aroma-taste interactions vary across individuals. The present study investigated how individual differences (gender, age, and sweet liker status) influenced the effect of aroma on sweetness intensity among young adults. An initial screening of five aromas, all congruent with sweet taste, for their sweetness enhancing effect was carried out using descriptive analysis. Among the aromas tested, vanilla was found most promising for its sweet enhancing effects and was therefore tested across three sucrose concentrations by 129 young adults. Among the subjects tested, females were found to be more susceptible to the sweetness enhancing effect of vanilla aroma than males. For males, the addition of vanilla aroma increased the sweet taste ratings significantly for the 22–25-year-olds, but not the 19–21-year-olds. Consumers were clustered according to their sweet liker status based on their liking for the samples. Although sweet taste ratings were found to vary with the sweet liker status, aroma enhanced the sweetness ratings similarly across clusters. These results call for more targeted product development in order to aid sugar reduction.

Sugar reduction in food and beverage products involves several challenges. Non-nutritive sweeteners may give unwanted off-flavors, while sugar-reduced products often lack mouthfeel. To overcome this, the addition of aroma to increase sweetness through cross-modal interactions, and the addition of hydrocolloids such as pectin to increase viscosity, have been suggested as strategies to aid sugar reduction. However, viscosity has been shown to decrease both taste and aroma intensities. An increase in viscosity may thereby affect the use of aromas as sweetness enhancers. Additionally, the effects of aromas and hydrocolloids on sweetness intensity and mouthfeel depend on the food matrix involved. The present study investigated cross-modal aroma–sweetness–viscosity interactions in two beverage matrices: water and apple nectar. The perceptual effects of vanilla aroma (0–1 mL/kg), sucrose (2.5%–7.5% w/w) and pectin (0%–0.3% w/w) were studied in both matrices. For each matrix, cross-modal interactions were analyzed with descriptive analysis using a trained sensory panel. The effect of vanilla aroma on sweetness intensity was found to be higher in apple nectar compared to in water. Furthermore, pectin affected neither taste, aroma, nor the cross-modal effects of aroma on taste in either of the matrices. These results indicate that pectin, in the studied range of concentrations, may be used to improve mouthfeel in sugar-reduced beverages, without compromising taste or aroma perception.

… cross modal interactions for … sweetness perception and reduced changes in consumer hedonic perception. These results showed the potential of aroma-related cross modal interactions …

… out-of-phase which resulted a sweetness intensity enhancement by more than 35% compared … Aroma-induced sweetness enhancement can be explained by cross-modal aroma-taste …

Perception of flavor is a dynamic process during which the concentration of aroma molecules at the olfactory epithelium varies with time as they are released progressively from the food in the mouth during consumption. The release kinetics depends on the food matrix itself, but also on food oral processing, such as mastication behavior and food bolus formation with saliva, for which huge inter-individual variations exist due to physiological differences. Sensory methods, such as time-intensity (TI), or the more recent methods temporal dominance of sensations (TDS) and temporal check-all-that-apply (TCATA), are used to account for the dynamic and time-related aspects of flavor perception. Direct injection mass spectrometry (DIMS) techniques that measure in real-time aroma compounds directly in the nose (nosespace), aimed at obtaining data that reflect the pattern of aroma release in real-time during food consumption, supposed to be representative of perception, have been developed since 25 years. Examples obtained with MS operated in chemical ionization mode at atmospheric or sub-atmospheric pressure (atmospheric pressure chemical ionization APCI or proton transfer reaction PTR) will be given, with emphases on studies conducted with simultaneous dynamic sensory evaluation. Inter-individual variations in terms of aroma release and their relevance for understanding flavor perception will be discussed, as well as evidenced cross-modal interactions.

Graphical abstract

Fruity aroma substances hold potential for enhancing the sensory properties of non-nutritive sweeteners. This study investigated the effects of six fruit-derived aroma compounds (isoamyl isovalerate, ethyl butyrate, isoamyl butyrate, ethyl 2-methylbutyrate, linalool, and phenethyl isobutyrate) on the sweetness and bitterness of Rebaudioside A (Reb A). Sensory evaluations revealed that these compounds significantly improved sweetness perception in 0.03 % Reb A solutions, with ethyl 2-methylbutyrate (1 mg/kg) exhibiting the strongest enhancement. T-I analysis demonstrated reduced bitterness intensity and duration, particularly for phenethyl isobutyrate. Molecular simulations indicated that aroma compounds lowered the binding free energy between Reb A and the T1R2 sweet receptor, stabilizing interactions via hydrogen bonds and steric hindrance. These findings elucidate the molecular mechanisms underlying odor-induced taste enhancement, offering practical strategies for optimizing Reb A's flavor profile in sugar-reduced products.

Artificial sensory analysis, electronic tongue analysis, cell model and molecular dynamics (MD) simulation were integrated to explore how sweet aroma compounds in sweet oranges affect the perceived sweetness of erythritol. Sensory analysis and cell model verified that γ-decanolactone has the best sweet-enhancing effect. MD simulations were carried out to reveal the mechanisms underpinning action of the erythritol-sweet taste receptor protein binary system and the ternary systems formed by γ-decanolactone with erythritol and sweet taste receptor proteins. The findings revealed that sweet aroma compounds could alter receptor protein conformational stability and key amino acid residue interactions, thus enhancing the binding stability of erythritol to sweet taste receptor proteins and improving human sweetness perception. The research offers a comprehensive summary of the connections among research methods for sugar-reducing sweet aroma substances, provides theoretical support for developing low-sugar and sugar-substitute foods in the food industry.

Background: Understanding how aroma compounds enhance monosodium glutamate (MSG) umami perception remains a critical challenge in flavor science. Methods: The umami-enhancing effects of meaty flavorings were investigated using nasal clip sensory evaluation (orthonasal blockage). Active aroma compounds were subsequently identified using gas chromatography-mass spectrometry (GC-MS). The three-dimensional structure of the umami receptor T1R1/T1R3 was constructed by homology modeling. The interaction mechanism was deciphered using molecular dynamics (MD) simulations. Results: Seafood essence S demonstrated the most potent umami enhancement. Five key compounds significantly intensified the MSG umami intensity: methional, dimethyl sulfide (DMS), D-limonene (DLE), 2,3-dimethylpyrazine, and dimethyl trisulfide. Notably, this enhancement persisted even under nasal clip conditions, revealing a novel mechanism independent of cross-modal interactions. Sulfur-containing compounds consistently demonstrated umami-enhancing effects across the evaluation conditions. MD simulations showed that aroma compounds induced allosteric remodeling of T1R1/T1R3, strengthening MSG-receptor hydrogen bonding (1.8–2.6-fold increase), reducing receptor flexibility, and stabilizing the ternary complex. Binding affinity was highest for DMS, followed by DLE and methional. Conclusion: This study provides the first receptor-level evidence that aroma compounds directly modulate MSG-taste receptor interactions through allosteric regulation, offering a novel theoretical framework for odor–taste interactions with significant implications for umami enhancer design and flavor research.

… of sweetness intensity due to sugar reduction, while aroma-induced sweetness enhancement … (4) Constructing a real food matrix and investigating the cross-modal interactions of taste, …

… sweetness in sucrose solutions. For instance, in an exploration of aromamediated cross-modal interactions … sweeteners (NNS) through aroma-induced sweetness remains scarce. This …

… cross-modal interaction highlights the role of odor information in modulating multisensory sweetness … stronger sweetening effects, and aroma-induced sweetening does not necessarily …

… to activate a receptor that does not depend on the combined expression of T1R2 and T1R3. In … a role in glucose sensing, T1R2 knock-out (KO) and T1R3 KO mice display normal chow …

… subsequent events in the activation of T1R2:T1R3 receptors, we show that both subunits … of binding sites on both T1R2 and T1R3? Or are distinct subsets of sweet stimuli more efficiently …

… The T1R family of taste receptors mediates 2 taste qualities: T1R2/T1R3 for sweet taste and … has lagged behind other sensory modalities, such as vision and olfaction. Great progress …

Rising living standards heighten the demand for healthier sugar-reduced foods. This study used Headspace Solid-Phase Microextraction (HS-SPME) and Gas Chromatography-Olfactometry-Mass Spectrometry (GC/O-AT) to analyze volatile components in sweet orange juice, identifying 12 key sweet aroma compounds. Sensory and electronic tongue evaluations indicated that seven sweetness-related odor substances- (E)-citral, (E)-β-farnesene, β-myrcene, tallo-ocimene, nonanal, citronellyl formate, and tallo-ocimene-significantly enhanced the sweetness of a 5 % sucrose solution. In contrast, while nonanol was found to have no sugar-reducing sweetness-enhancing effect. Furthermore, molecular docking analysis was employed to examine the regions, binding energies, and interaction forces between eight sweet and fragrant aroma compounds from sweet orange and the T1R2-T1R3 sweet taste receptor-sucrose ternary system. The average binding energies with the receptor were -3.2 kcal/mol, -1.2 kcal/mol, -3.0 kcal/mol, -1.6 kcal/mol, -5.9 kcal/mol, -5.8 kcal/mol, -3.6 kcal/mol, and -6.0 kcal/mol, respectively. However, it should be noted that binding energy alone is not the sole criterion for judging the sweetening effect. Molecular dynamics (MD) results further demonstrated that the stability of the binding between sucrose and the sweet taste receptor was improved under the influence of (E)-citral, with the interaction between the two relying on hydrogen bonds, water bridges, and hydrophobic forces. This provides a theoretical basis for validating the sweetness-enhancing effects of aroma substances and insights into novel sweetener development.

Simple sugars are thought to elicit a unitary sensation, principally via the "sweet" taste receptor type 1 taste receptor (T1R)2+T1R3, yet we previously found that rats with experience consuming two metabolically distinct sugars, glucose and fructose, subsequently licked more for glucose than fructose, even when postingestive influences were abated. The results pointed to the existence of an orosensory receptor that binds one sugar but not the other and whose signal is channeled into neural circuits that motivate ingestion. Here we sought to determine the chemosensory nature of this signal. First, we assessed whether T1R2 and/or T1R3 are necessary to acquire this behavioral discrimination, replicating our rat study in T1R2+T1R3 double-knockout (KO) mice and their wild-type counterparts as well as in two common mouse strains that vary in their sensitivity to sweeteners [C57BL/6 (B6) and 129X1/SvJ (129)]. These studies showed that extensive exposure to multiple concentrations of glucose and fructose in daily one-bottle 30-min sessions enhanced lick responses for glucose over fructose in brief-access tests. This was true even for KO mice that lacked the canonical "sweet" taste receptor. Surgical disconnection of olfactory inputs to the forebrain (bulbotomy) in B6 mice severely disrupted the ability to express this experience-dependent sugar discrimination. Importantly, these bulbotomized B6 mice exhibited severely blunted responsiveness to both sugars relative to water in brief-access lick tests, despite the fact that they have intact T1R2+T1R3 receptors. The results highlight the importance of other sources of chemosensory and postingestive inputs in shaping and maintaining "hardwired" responses to sugar.

… is mediated by the remaining T1R2 or T1R3 acting as a homodimer receptor, although only the T1R3 subunit appears to function as a low-affinity sugar receptor in normal mice (Damak …

The characteristic aroma compounds of five-fold sweet orange oil were analyzed using gas chromatography-mass spectrometry combined with the odor aroma value (OAV) method. The results indicated that limonene, linalool, dodecanol, (E,E)-2,4-decadienal, (E)-citral, linalool, (E)-2-decenal, and geraniol are important contributors. The sweetening effects of key compounds on sucrose solutions were experimentally investigated. The results showed that the sweetness effects of five compounds (limonene, citronellal, geraniol, β-sinensal and β-caryophyllene) were better than those of (E)-citral, linalool and octanal. Molecular dynamics implied that the hydrogen bonding residues of the T1R2/T1R3-sucrose system were converted from LYS65, GLU302, ASP278, and SER144 to ASP278, SER144, ASP142, and ASP213 after the addition of limonene. Meanwhile, the hydrophobic interaction forces of the system are significantly enhanced. The total energy of the T1R2/T1R3-sucrose system decreased from -32.08 kcal/mol to -63.57 kcal/mol. The synergistic sweetening mechanism of characteristic aroma compounds of sweet orange oil on sucrose was revealed.

… Specifically, when a strawberry odor was presented with sucrose and subjects were instructed to rate fruitiness as well as sweetness, enhancement of sweetness was nil. This pivotal …

It is assumed “Non-volatile” tastes like sucrose do not activate retro nasal pathways. Recent studies find that sucrose when aerosolized, can reach the retro nasal olfactory region and be perceived. The neural mechanisms by which the human brain interprets sucrose via retro nasal pathways is unknown. We examined neural activity to sucrose with a nose clip on (blocking retro nasal) and nose clip off, in healthy adults (N=34, mean 25 yrs.). We examined the whole brain and ROIs involved in taste, smell, attention, reward and multi-modal integration; insula, postcentral gyrus, amygdala, olfactory cortex, subgenual and pregenual anterior cingulate, nucleus accumbens and OFC. We also examined correlations with subjective ratings of pleasantness and mouth fullness. We also examined the effect of the nose clip on the time to peak activity for sucrose using the bold signal time course. The nose clip on vs off reduced the subjective experience of mouth fullness. Neural activity to sucrose was reduced with the nose clip on in the primary taste, olfactory, attention and reward ROIs and in the rolandic operculum, lingual gyrus and precuneus in the whole brain analyses. The olfactory and prefrontal cortex ROIs tracked subjective mouth fullness, but this was not apparent with the nose clip on. Blocking retro nasal sensation reduces subjective and neural responses to sucrose taste. Retro nasal sensations could play a role in “pure” taste perception. Developing more satisfying low-sugar foods could be achieved by enhancing the perception of sweetness through aroma modulation.

This study employed time‐intensity and temporal dominance of sensations analyses to quantify the contribution of the retronasal pathway to sweet perception by comparing the dynamic perception of sucrose and rebaudioside A (Reb A) under conditions with and without a nose‐clip (which physically blocks the retronasal pathway). Results showed that blocking the retronasal pathway significantly reduced both the intensity and duration of sweetness for sucrose and Reb A. Analysis using the newly developed “retro‐taste partition coefficient” revealed distinct temporal patterns of retronasal dependency: Reb A exhibited a higher retronasal contribution in the early phase of perception, whereas sucrose demonstrated a significantly stronger dependency during the later stages. Compared to sucrose, Reb A still shows perceptible gaps in sweetness quality and temporal profile. Furthermore, Reb A elicited pronounced bitterness and astringency, which became more pronounced during the later stages of perception when the retronasal pathway was blocked. This study highlights the critical role of the retronasal pathway in sweet perception and provides a temporal‐dynamic analytical framework along with quantitative tools for the sensory optimization of sweetener formulations.

… enhanced by sweet taste, but not by sour or bitter taste. This raises questions regarding the underlying conditions of retronasal odor enhancement … substances (eg, sweet carbohydrate), …

This study investigated how the retro‐nasal sensation of sweeteners is centrally processed by examining brain activities using electroencephalography (EEG) technique. Interactions effects were found between the event‐related potentials (ERP) and nasal conditions (nose‐plug‐on or ‐off) at the electrode sites of C3, C4, CP3, and FC4. Retro‐nasal sensation seems to increase P1 amplitudes of rebaudioside A and P1 latencies of pure water at the C1–C3–C5–CP3–FC3 clusters, and shorten the P3 latencies of sucrose and rebaudioside A at the C2–C4–C6–CP4–FC4 clusters. Furthermore, the stimuli's ERP components only differed when retro‐nasal sensation was allowed (nose‐plug‐off). Combing the above evidence, we intend to conclude that rebaudioside A and sucrose in the form of aerosol particles can be retro‐nasally sensed and these sensations facilitate their recognition or evaluation (implied by their lower P3 latencies in the presence of retro‐nasal sensation), and shape their differences at the early cognitive process (implied by their differed P1 amplitudes).

… sweet taste significantly enhanced the processing of a congruent olfactory stimulus when presented through the retronasal … applied during orthonasal olfaction seemed to induce conflict …

The impact of olfactory perception on sweetness was explored in a model solution using odorants at subthreshold concentrations. First, the impact of 6 odorants, previously described in the literature as congruent with sweetness, was investigated at suprathreshold level in a sucrose solution. Ethyl butyrate and maltol were selected as they had the highest and the lowest sweetness-enhancing properties, respectively. Second, the impact on sweetness of the 2 odorants was investigated at subthreshold concentrations. A system delivering a continuous liquid flow at the same sucrose level, but with varying odorant concentrations, was used. At a subthreshold level, ethyl butyrate but not maltol significantly enhanced the sweetness of the sucrose solution. This study highlights that olfactory perception induced by odorants at a subthreshold level can significantly modulate taste perception. Finally, contrary to results observed with ethyl butyrate at suprathreshold levels, at subthreshold levels, the intensity of sweetness enhancement was not proportional to ethyl butyrate concentration.

… Lastly, there was no evidence for gustatory sweetness enhancement when the flavor had an orthonasal “sweet” odor, such as the banana flavor or the green apple flavor to which maltol…

… of sweetness reported by participants. Specifically, as reflected in the enhancement of sweetness by retronasal aroma, sweetness … dependent on the sweet tastants contained in foods. …

… Odor-induced taste enhancement (OITE) is a phenomenon … perceptual routes (orthonasal or retronasal), odor concentration, … molecules with potent taste enhancement effects and the …

BackgroundCommon foods consist of several taste qualities. Consumers perceive intensity of a particular taste quality after noticing it among other taste qualities when they eat common foods. We supposed that while one is eating the facility for noticing a taste quality present in a common food will differ among taste qualities which compose the common food. We, therefore, proposed a new measurement scale for food perception named ‘noticeability’. Furthermore, we found that consumers’ food perceptions to common foods were modified by retronasal aroma. In this study, in order to examine whether retronasal aroma affects the relationship between noticeability and perceived intensity for taste, we evaluated participants for noticeability and perceived intensity of five fundamental taste qualities (sweetness, saltiness, sourness, bitterness, and umami) under open and closed nostril conditions using one of the most popular traditional Japanese confections called ‘yokan’.ResultsThe taste quality showed that the highest noticeability and perceived intensity among five fundamental taste qualities for yokan was sweetness, independent of the nostril condition. For sweetness, a significant decrease of correlation between noticeability and perceived intensity was observed in response to retronasal aroma. On the other hand, for umami, correlation between noticeability and perceived intensity significantly increased with retronasal aroma.ConclusionsAs the retronasal aroma of yokan allowed feature extraction from taste by Japanese consumers, we reconfirmed that consumers’ food perceptions were modified by the retronasal aroma of a common food.

… in the congruent (sweet-taste) condition. Interestingly, the simultaneous sweet gustatory … case of congenitally blind subjects, olfactory perception is generally enhanced while taste is …

… Sweetness enhancement emerged only at 5 s, indicating a short-lived expectancy-driven effect, whereas saltiness enhancement … -drinking sequence (ie, retronasal odor + post-drinking) …

During food consumption, tastes combine with retronasal odours to form flavour, which leads to a link so robust that retronasal odours can elicit taste sensations without concurrent taste stimulation. However, the cortical integration of these parallel sensory signals remains unclear. Here, we combine a flavour-binding paradigm and functional neuroimaging to test whether retronasal odorants evoke encoding patterns in the insula similar to those of their paired tastants. Healthy participants attended a familiarisation session with congruent sweet and savoury flavours followed by two fMRI sessions where they separately received the constituent tastants and odorants. Multivariate pattern analysis revealed classification of retronasal odours within the insula, exhibiting overlapping representations with their associated tastes, particularly in the ventral anterior insula. Additionally, we observed temporal instability in insular taste representations, paralleling findings in rodent gustatory cortex. These findings underscore the robust integration of gustatory and retronasal olfactory processing that underpin the flavour percept.

This study investigated the sweetness-enhancing effects of nine sweet aroma compounds from sweet orange on 5% sucrose solution. Through static sensory evaluations and electronic tongue analysis, carveol was found to enhance sweetness most significantly (28.8%), followed by γ-decalactone (23.2%), γ-nonalactone (23.0%), and δ-decalactone (20.0%). By using the time-intensity method for dynamic sensory evaluation, it was shown that the perception of sweetness increased rapidly and the duration was slightly prolonged after the addition of sweet aroma compounds. Molecular docking showed a binding free energy of −5.9 kcal/mol for the T1R2/T1R3-sucrose complex. Ternary complexes with added aromatic compounds had substantially lower energies (−8.62 to −10.5 kcal/mol), indicating enhanced receptor-ligand affinity. Molecular dynamics results showed that the addition of aromatic compounds led to the decrease in the binding energy of the T1R2/T1R3-sucrose system, the enhancement of hydrogen bonds and hydrophobic interactions, and the stabilization of dynamic changes in protein conformation.

Odor-induced sweetness enhancement (OISE) is an effective approach to lower sugar intake. In this study, static and dynamic sensory evaluations, combined with molecular docking, were used to explore the mechanism underlying sweetness enhancement in fructose solutions induced by watermelon juice odor compounds. Sensory evaluation results showed that the seven volatile odor compounds (VOCs) (ethyl acetate, ethyl propionate, octanal, (E,E)-2,4-hexadienal, (E)-2-octenal, methyl heptenone, and geranyl acetone) from watermelon juice could significantly increase the sweetness intensity of a 2.5% fructose solution, and the potency of OISE was significantly enhanced within 10 s. (E,E)-2,4-hexadienal, ethyl propionate, and methylheptenone showed the most significant OISE effects, which aligned with the sensory preference results. Further, molecular docking was used to explore the interactions between VOCs, fructose, and sweet receptors. The results showed that T1R2 was the main receptor for binding fructose and VOCs, and the interaction forces were primarily hydrogen bonds and hydrophobic interactions. In the presence of VOCs, the amino acid residues that formed hydrogen bonds with fructose were highly repetitive, with the main difference being the bond length, indicating the important role of flavor–sweetener receptor interactions in lowering fructose content and enhancing sweetness perception. Thus, this study provides a scientific basis for developing sugar-reduction technology based on aroma, in addition to enhancing sweetness.

… , molecular docking was used to analyze the binding energies and interactions between these compounds and olfactory receptors (… these compounds at the six receptors were −6.2 kcal/…

… In this study, four aldehyde aroma compounds found in sweet orange, including decanal, nonanal, octanal, and hexanal, (Xiao et al. 2024a, b) are investigated. Therefore, the objectives …

Yeast extract (YE) is derived from the soluble component in yeast cells, which is rich in peptides and has been used as a sweet-enhancing agent. It has the potential to be utilized to produce natural sweet-flavored peptides or sweet-enhancing peptides. To study the synergistic effect and mechanism of sweetness-enhancing peptides derived from YE, ultrafiltration fraction with molecular weight less than 1 kDa was screened according to sensory analysis, which showed a synergistic sweetening effect in stevioside and mogroside solution. Twenty potential taste peptides were identified from the screened fractions, among which EV, AM, AVDNIPVGPN and VDNIPVGPN showed sweetness-enhancing effects on both stevioside and mogroside. The sweetener-receptor-peptide complex was constructed to investigate the interaction of stevioside and mogroside to taste receptor type 1 member 2 accompanied by these peptides. The results of the molecular docking indicated that new hydrophobic interactions (Leu 279, Pro 308, Val 309, etc.) and hydrogen bonds (Ser 40, Ala 43, Asp 278, etc.) were formed between sweeteners and active sites in the venus flytrap domain. In conclusion, the presence of sweetness-enhancing peptides from YE improved the binding stability of sweeteners and receptors by increasing the binding interaction, especially the hydrophobic interactions, which contribute to the synergistic effect of sweetness-enhancing peptides.

This study investigates the sweetening effect of ten acids from sweet orange on 5% sucrose solution. It was discovered that 2-methylbutyric acid and 3-methylbutyric acid notably enhanced sweetness, whereas decanoic acid significantly reduced sweetness. Acetic acid, propionic acid and butyric acid sweetened slightly at low concentration, but inhibited sweetness at high concentration. Hexanoic and octanoic acids enhanced sweetness but reduced comfort. Nonanoic acid and trans-2-hexenoic acid did not significantly affect sweetness. The results of molecular docking revealed that hydrogen bonding and hydrophobic interactions were crucial for the binding of sucrose to the sweet taste receptor T1R2/T1R3. It has also found that LYS65, ASP278, SER165, GLU302, ASP142, and SER303 were key amino acids for sweetness. A 100 ns molecular dynamic simulation indicated that the addition of 2-methylbutyric acid stabilizes the sucrose-T1R2/T1R3 complex via extensive hydrogen bonding and water bridges. This findings pave the way for developing low-sugar orange juice beverages by leveraging aroma substances to augment sweetness. Graphical abstract.

… It is, therefore, likely that taste and smell receptors have … molecular modeling and other computational approaches. … used as templates for sweet and umami structure modeling.82 Very …

Mammalian sensory systems detect sweet taste through the activation of a single heteromeric T1R2/T1R3 receptor belonging to class C G-protein-coupled receptors. Allosteric ligands are known to interact within the transmembrane domain, yet a complete view of receptor activation remains elusive. By combining site-directed mutagenesis with computational modeling, we investigate the structure and dynamics of the allosteric binding pocket of the T1R3 sweet-taste receptor in its apo form, and in the presence of an allosteric ligand, cyclamate. A novel positively charged residue at the extracellular loop 2 is shown to interact with the ligand. Molecular dynamics simulations capture significant differences in the behavior of a network of conserved residues with and without cyclamate, although they do not directly interact with the allosteric ligand. Structural models show that they adopt alternate conformations, associated with a conformational change in the transmembrane region. Site-directed mutagenesis confirms that these residues are unequivocally involved in the receptor function and the allosteric signaling mechanism of the sweet-taste receptor. Similar to a large portion of the transmembrane domain, they are highly conserved among mammals, suggesting an activation mechanism that is evolutionarily conserved. This work provides a structural basis for describing the dynamics of the receptor, and for the rational design of new sweet-taste modulators.

… : they are not only chemesthetic stimuli but also volatile odorants and/or taste-active molecules. … as a sweet taste modulator by binding to the T1R2/T1R3 sweet receptor heterodimer, as …

Sucrose provides both sweetness and energy by binding to both Venus flytrap domains (VFD) of the heterodimeric sweet taste receptor (T1R2/T1R3). In contrast, non-caloric sweeteners such as sucralose and aspartame only bind to one specific domain (VFD2) of T1R2, resulting in high-intensity sweetness. In this study, we investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites: VFD2, VFD3, transmembrane domain 2 (TMD2), and TMD3 through binding experiments and computational docking studies. Our docking results reveal multiple binding sites for the tested ligands, including the radiolabeled ligands. Our experimental evidence demonstrates that the C20 carboxy terminus of the Gα protein can bind to the intracellular region of either TMD2 or TMD3, altering GPCR affinity to the high-affinity state for steviol glycosides. These findings provide a mechanistic understanding of the structure and function of this heterodimeric sweet taste receptor. Sucrose and other non-caloric sweeteners can bind to different domains of the heterodimeric sweet taste receptor (T1R2/T1R3), resulting in different levels of sweetness. Here, the authors investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites of T1R2/T1R3 through binding experiments and computational docking studies, revealing multiple binding sites for the tested ligands and structural– function correlations of ligand–receptor interactions.

Aldehydes are natural volatile aroma compounds generated by the Maillard reaction of sugars and amino acids in food and affect the flavor of food. They have been reported to exert taste-modifying effects, such as increases in taste intensity at concentrations below the odor detection threshold. The present study examined the taste-enhancing effects of short-chain aliphatic aldehydes, such as isovaleraldehyde (IVAH) and 2-methylbutyraldehyde, attempted to identify the taste receptors involved. The results obtained revealed that IVAH enhanced the taste intensity of taste solutions even under the condition of olfactory deprivation by a noseclip. Furthermore, IVAH activated the calcium-sensing receptor CaSR in vitro. Receptor assays on aldehyde analogues showed that C3-C6 aliphatic aldehydes and methional, a C4 sulfur aldehyde, activated CaSR. These aldehydes functioned as a positive allosteric modulator for CaSR. The relationship between the activation of CaSR and taste-modifying effects was investigated by a sensory evaluation. Taste-modifying effects were found to be dependent on the activation state of CaSR. Collectively, these results suggest that short-chain aliphatic aldehydes function as taste modulators that modify sensations by activating orally expressed CaSR. We propose that volatile aroma aldehydes may also partially contribute to the taste-modifying effect via the same molecular mechanism as kokumi substances.

Chemical communication is based on the release of chemical cues, including odorants, tastants and semiochemicals, which can be perceived by animals and trigger physiological and behavioral responses. These compounds exhibit a wide size and properties range, spanning from small volatile molecules to soluble proteins, and are perceived by various chemosensory receptors (CRs). The structure of these receptors is very well conserved across all organisms and within the family to which they belong, the G-protein-coupled receptor (GPCR) family. It is characterized by highly conserved seven-transmembrane (7TM) α-helices. However, the characteristics of these proteins and the methods used to study their structures are limiting factors for resolving their structures. Due to the importance of CRs—especially olfactory and taste receptors, responsible for two of our five basic senses—alternative methods are utilized to overcome these structural challenges. Indeed, in silico structural biology is an expanding field that is very useful for CR structural studies. Since the 1960s, many algorithms have been developed and improved in an attempt to resolve protein structure. We review the current knowledge regarding different vertebrate CRs in this study, with an emphasis on the in silico structural methods employed to improve our understanding of CR structures.

… by action of a sweetener receptor positive allosteric modulator (PAM) has been achieved … (7-TMD) proteins named T1R2 and T1R3, and named the receptor T1R2/T1R3. They also …

Sweet taste, one of the five basic taste qualities, is not only important for evaluation of food quality, but also guides the dietary food choices of animals. Sweet taste involves a variety of chemical compounds and structures, including natural sugars, sugar alcohols, natural and artificial sweeteners, and sweet-tasting proteins. The preference for sweetness has induced the over-consumption of sugar, contributing to certain prevailing health problems, such as obesity, diabetes and cardiovascular disease. Non-nutritive sweeteners, including natural and synthetic sweeteners, and sweet-tasting proteins have been added to foods to reduce the caloric intake from sugar, but many of these sugar substitutes induce an off-taste or after taste that negatively impacts any pleasure derived from the sweet taste. Sweet taste is detected by sweet taste receptor, that also play an important role in the metabolic regulation of the body, such as glucose homeostasis and incretin hormone secretion. In this review, the role of sweet tastants and the sweet taste receptors involved in sweetness perception, and their effect on obesity and diabetes are summarized. Sweet taste enhancement, as a new way to solve the over-consumption of sugar, is discussed in this contribution. Sweet taste enhancers can bind with sweet tastans to potentiate the sweetness of food without producing any taste by itself. Various type of sweet taste enhancers, including synthetic compounds, food-processed substances and aroma compounds, are summarized. Notably, few natural, non-volatile compounds have been identified as sweetness enhancers.

… -omics, in vitro gut systems, and AI-… flavour profiles with microbial dynamics, this review outlines strategies for designing functional foods that are both sensorially engaging and health-…

… responses that affect gastrointestinal function, … by taste receptors along the gut plays a key role in the process of digestion, and how disturbances or adaptations of these chemosensory …

The ability of humans to sense chemical signals in ingested substances is implicit in the ability to detect the five basic tastes; sweet, sour, bitter, salty, and umami. Of these, sweet, bitter, and umami tastes are detected by lingual G-protein-coupled receptors (GPCRs). Recently, these receptors were also localized to the gut mucosa. In this review, we will emphasize recent advances in the understanding of the mechanisms and consequences of foregut luminal chemosensing, with special emphasis on cell surface GPCRs such as the sweet and proteinaceous taste receptors (TASRs), short- and long-chain fatty acid (FA) receptors, and bile acid receptors. The majority of these luminal chemosensors are expressed on enteroendocrine cells (EECs), which are specialized endocrine cells in the intestine and pancreas that release gut hormones with ligand activation. These gut hormones are responsible for a wide variety of physiologic and homeostatic mechanisms, including glycemic control, appetite stimulation and suppression, regulation of gastric emptying, and trophic effects on the intestinal epithelium. Released from the EECs, the gut peptides have paracrine, autocrine, and endocrine effects. Additionally, EECs have unique direct connections to the enteric nervous system enabling precise transmission of sensory data to and communication with the central nervous system. We will also describe how gut sensors are implicated in gut hormone release, followed by examples of how altered gut chemosensing has been implicated in pathological conditions such as metabolic diseases including diabetes and obesity, functional dyspepsia, helminthic infections, colitis, gastric bypass surgery, and gastric inflammation and cancer.

G protein-coupled receptors (GPCRs) belong to the largest class of drug targets. Approximately half of the members of the human GPCR superfamily are chemosensory receptors, including odorant receptors (ORs), trace amine-associated receptors (TAARs), bitter taste receptors (TAS2Rs), sweet and umami taste receptors (TAS1Rs). Interestingly, these chemosensory GPCRs (csGPCRs) are expressed in several tissues of the body where they are supposed to play a role in biological functions other than chemosensation. Despite their abundance and physiological/pathological relevance, the druggability of csGPCRs has been suggested but not fully characterized. Here, we aim to explore the potential of targeting csGPCRs to treat diseases by reviewing the current knowledge of csGPCRs expressed throughout the body and by analysing the chemical space and the drug-likeness of flavour molecules.

Background Metabolic syndrome is a major public health issue, increasing the risk of type 2 diabetes and cardiovascular disease. While traditional dietary strategies focus on …

Abstract Previous fMRI research identified superior temporal sulcus as central integration area for audiovisual stimuli. However, less is known about a general multisensory integration network across senses. Therefore, we conducted activation likelihood estimation meta-analysis with multiple sensory modalities to identify a common brain network. We included 49 studies covering all Aristotelian senses i.e., auditory, visual, tactile, gustatory, and olfactory stimuli. Analysis revealed significant activation in bilateral superior temporal gyrus, middle temporal gyrus, thalamus, right insula, and left inferior frontal gyrus. We assume these regions to be part of a general multisensory integration network comprising different functional roles. Here, thalamus operate as first subcortical relay projecting sensory information to higher cortical integration centers in superior temporal gyrus/sulcus while conflict-processing brain regions as insula and inferior frontal gyrus facilitate integration of incongruent information. We additionally performed meta-analytic connectivity modelling and found each brain region showed co-activations within the identified multisensory integration network. Therefore, by including multiple sensory modalities in our meta-analysis the results may provide evidence for a common brain network that supports different functional roles for multisensory integration.

… Starting from pieces of evidence for the integration of olfactory and gustatory information at sub- and suprathreshold levels, we review the mechanisms underpinning aroma–taste …

There is a drive to increase the acceptability of sweeteners such as stevia in foods and reduce any off tastes or bitterness. One way to do this is to add flavour modifiers. We have shown previously that adding a flavour modifier to the artificial sweetener sucralose resulted in synergistic neural activity which could underpin improved taste sensation. Therefore, the aim of this study was to see if adding a flavour modifier to stevia would also reveal synergistic neural effects. Healthy adults (N = 34, Mean age 25 yrs.) participated in a within-subjects study examining the neural effects of stevia plus a flavour modifier vs stevia alone and vs sucrose. We examined whole brain data, and insula, postcentral gyrus, and hypothalamus ROIs identified from meta-analysis on brain responses to sweet tastes. We also examined the ROIs NAcc and amygdala given their role in reward and aversion processing. We examined the relationships between brain activity and the subjective ratings of pleasantness, bitterness and mouth fullness for the tastes. Super-additive neural effects to stevia plus modifier were found in the postcentral gyrus, parietal cortex and the occipital gyrus at the whole brain level, p < 0.05 Family Wise Error corrected threshold. In the ROI analysis we found reduced activation of the hypothalamus to the stevia plus modifier condition vs stevia p = 0.008 and higher postcentral gyrus activation to sucrose vs stevia p = 0.01. We found the insula tracked the pleasantness of the stevia conditions. The hypothalamus tracked the pleasantness and mouth fullness of the stevia plus modifier but not the stevia and the NAcc tracked the mouth fullness of the stevia plus modifier more than stevia. Further the amygdala tracked the bitterness of the stevia but not the stevia plus modifier. This study offers the first evidence that combining stevia with a flavour modifier reveals synergistic neural activity in brain areas associated with taste sensation, intensity and multisensory integration. Further we show that adding a modifier to stevia could increase unconscious desirability for stevia outside of subjective awareness by masking its bitterness and increasing its mouth fullness.

… One of the striking aspects of multisensory flavor perception … A nascent field of neuroimaging research has also started to … less sweet than expected, enhanced reported sweetness and …

Our hedonic response to a food is determined by its flavor, an inherently multisensory experience that extends beyond the mere addition of its odor and taste. While congruency is known to be important for multisensory processes in general, little is known about its specific role in flavor processing. The aim of the present study was to delineate the effects of odor-taste congruency on two central aspects of flavor: odor referral (or mislocalization) to the mouth, and pleasantness. We further aimed to test whether an eventual effect on pleasantness was mediated by odor referral. Aqueous solutions containing odors and tastes were prepared to create food-like stimuli with varying degrees of congruency, ranging from maximally incongruent to maximally congruent in nine steps. Thirty participants reported where they perceived the odors, and how much they liked the solutions. Congruency had a positive linear effect both on odor referral to the oral cavity and on pleasantness. However, the effect of congruency on pleasantness was not mediated by odor referral. These results indicate that as an odor-taste mixture approximates a mental representation of a familiar food, its components are increasingly merged into one perceptual object sensed in the mouth. In parallel, the mixture is evaluated as increasingly pleasant, which promotes consumption of familiar foods that have been determined through experience to be non-toxic. While the modulatory role of congruency on pleasantness and odor referral was confirmed, our results also indicate that these effects arise through distinct perceptual mechanisms.

ABSTRACT Objectives There is a significant need to reduce sugar in food. We can replace sugar with non-nutrient sweeteners; however, they need to be desirable. Previously, we found adding a flavour modifier to a taste can result in neural super-additivity that could drive enhanced pleasure. It is not known if adding a flavour modifier to a non-nutrient sweetener could affect brain activity in the same way. Methods Healthy adults (N = 48, Mean age 26 yrs.) participated. We examined the neural effects of adding a flavour modifier to the non-nutrient sweetener sucralose (SLM) and the neural effects of sucrose vs sucralose. We examined whole brain data and the ROIs insula, pre- and postcentral gyrus, identified from a meta-analysis on brain responses to sweet tastes. Results Super-additive neural effects to SLM were in the mid/inferior temporal gyri, pre- and post-central gyri and parietal areas at the whole-brain level, p < 0.05 Family Wise Error corrected threshold. Superior frontal gyrus activity correlated with SLM pleasantness. There were no whole brain differences including reward-related differences between sucrose and sucralose. We did find greater ROI somatosensory activity (p = 0.01) for sucrose vs sucralose. Discussion We provide the first evidence that adding a flavour modifier to a non-nutrient sweetener reveals synergistic neural activity in brain areas associated with taste sensation, intensity, attention, perception and multisensory integration. Modifiers added to sweeteners could help consumers switch to healthier options and producers reduce the amount of sugar in foods. Future studies should examine if neural super-additivity effects can be used to predict subsequent consummatory behaviour.