Unveiling the Immunomodulatory Potential of Phenolic Compounds in Food Allergies.

Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.

Mass spectrometry-based quantification of immunostimulatory gliadin proteins and peptides in coloured wheat varieties: Implications for Celiac Disease.

Pigmented wheat varieties (Triticum aestivum spp.) are getting increasingly popular in modern nutrition and thoroughly researched for their functional and nutraceutical value. The colour of these wheat grains is caused by the expression of natural pigments, including carotenoids and anthocyanins, that can be restricted to either the endosperm, pericarp and/or aleurone layers. While contrasts in phytochemical synthesis give rise to variations among purple, blue, dark and yellow grain's antioxidant and radical scavenging capacities, little is known about their influence on gluten proteins expression, digestibility and immunogenic potential in a Celiac Disease (CD) framework. Herein, it has been found that the expression profile and immunogenic properties of gliadin proteins in pigmented wheat grains might be affected by anthocyanins and carotenoids upregulation, and that the spectra of peptide released upon simulated gastrointestinal digestion is also significantly different. Interestingly, anthocyanin accumulation, as opposed to carotenoids, correlated with a lower immunogenicity and toxicity of gliadins at both protein and peptide levels. Altogether, this study provides first-level evidence on the impact modern breeding practices, seeking higher expression levels of health promoting phytochemicals at the grain level, may have on wheat crops functionality and CD tolerability.

Evidence of increased gluten-induced perturbations in the nucleophilic tone and detoxifying defences of intestinal epithelial cells impaired by gastric disfunction.

It has been increasingly demonstrated over the past few years that some proteolytically resistant gluten peptides may directly affect intestinal cell structure and functions by modulating pro-inflammatory gene expression and oxidative stress. The relationship between oxidative cell damage and Celiac Disease (CD) is supported by several studies on human intestinal epithelial cell lines, such as the Caco-2 cell model, already shown to be particularly sensitive to the pro-oxidative and pro-apoptotic properties of gluten protein digests. Through providing valuable evidence concerning some of the pathophysiological mechanisms that may be at play in gluten-related disorders, most of these in vitro studies have been employing simplified digestion schemes and intestinal cell systems that do not fully resemble mature enterocytes in terms of their characteristic tight junctions, microvilli and membrane transporters. Herein the peptide profile and pro-oxidative effect of two different gastrointestinal gliadin digestions was thoroughly characterized and comprehensively compared: one following the complete INFOGEST workflow and a second one by-passing gastric processing, to assess the dependence of gliadin-triggered downstream cell effects on pepsin activity. In both matrices, gluten-derived immunogenic peptide sequences were identified by non-targeted LC-MS/MS. Altogether, this study provides first-hand data concerning the still unexplored peptide composition, gastric-dependence and immunogenicity of physiologically representative gliadin protein digests as well as foundational clues stressing the need for more complex and integrated in vitro cell systems when modelling and exploiting gluten-induced perturbations in the nucleophilic tone and inflammatory status of intestinal epithelial cells.

Characterization of the Effect of a Novel Production Technique for 'Not from Concentrate' Pear and Apple Juices on the Composition of Phenolic Compounds.

The consumption of 'not-from-concentrate' (NFC) fruit juices can be a convenient and enjoyable way to incorporate the nutritional benefits and flavors of fruits into one's diet. This study will focus on the effect of production of juices from apple and pear fruits, by using centrifugal decanter and tangential filtration, on the profile of polyphenols as a valuable source of bioactive compounds. Likewise, by-products from the juice industry were characterized in order to understand the high-value-added potential based on their composition of polyphenols. Briefly, apple and apple juice showed great contents of chlorogenic acid (0.990 ± 0.021 mg/g of DW), the dihydrochalcone phloridzin (1.041 ± 0.062 mg/g of DW), procyanidins (0.733 ± 0.121 mg/g of DW) and quercetin derivatives (1.501 ± 0.192 mg/g of DW). Likewise, the most abundant compounds in pear and pear juices were chlorogenic acid (0.917 ± 0.021 mg/g of DW), caffeoylquinic acid (0.180 ± 0.029 mg/g of DW), procyanidins (0.255 ± 0.016 mg/g of DW) and quercetin derivatives (0.181 ± 0.004 mg/g of DW). Both temperature and tangential speed affect the amount of phenolic compounds in fruit juices, highlighting the need to control the technological process to obtain a more nutritious/healthier beverage. Overall, NFC juices arise as a better option when compared with concentrated juices. Furthermore, the higher yield of phenolic compounds found in fruit pomace clearly open new ways for upcycling this fruit by-product as a high-value-added ingredient.

Anthocyanins as Immunomodulatory Dietary Supplements: A Nutraceutical Perspective and Micro-/Nano-Strategies for Enhanced Bioavailability.

Anthocyanins (ACNs) have attracted considerable attention for their potential to modulate the immune system. Research has revealed their antioxidant and anti-inflammatory properties, which play a crucial role in immune regulation by influencing key immune cells, such as lymphocytes, macrophages, and dendritic cells. Moreover, ACNs contribute towards maintaining a balance between proinflammatory and anti-inflammatory cytokines, thus promoting immune health. Beyond their direct effects on immune cells, ACNs significantly impact gut health and the microbiota, essential factors in immune regulation. Emerging evidence suggests that they positively influence the composition of the gut microbiome, enhancing their immunomodulatory effects. Furthermore, these compounds synergize with other bioactive substances, such as vitamins and minerals, further enhancing their potential as immune-supporting dietary supplements. However, detailed clinical studies must fully validate these findings and determine safe dosages across varied populations. Incorporating these natural compounds into functional foods or supplements could revolutionize the management of immune-related conditions. Personalized nutrition and healthcare strategies may be developed to enhance overall well-being and immune resilience by fully understanding the mechanisms underlying the actions of their components. Recent advancements in delivery methods have focused on improving the bioavailability and effectiveness of ACNs, providing promising avenues for future applications.

New insights into the oral interactions of different families of phenolic compounds: Deepening the astringency mouthfeels.

Astringency is a tactile sensation of puckering, tightening and dryness in the oral cavity, commonly induced by polyphenols. In this study, the interaction of two phenolic compound mixtures, one rich in gallotannins and the other in flavonols, with two oral models (tongue (HSC3) or buccal mucosa (TR146) was evaluated. Results provided evidence that gallotannins and flavonols seem to bind in a different way to the different oral constituents and models used. Gallotannins seems to bind more to the tongue than to the buccal mucosa cell line, but this difference is overcome by the presence of salivary proteins. Conversely, for the flavonol mixture, the presence of salivary proteins seems to restrain the interaction with oral cell lines. Structure-binding activity relationships were evidenced within each mixture: for gallotannins, interactions seem to increase along with the galloylation degree while for flavonol it was observed that increasing numbers of glucose residues decreased the binding activity.

Understanding the molecular interactions between a yeast protein extract and phenolic compounds.

Phenolic compounds are partially removed during fining, which may influence the organoleptic properties of beverages. Among phenolic compounds, tannins have been widely associated to the taste of beverages (namely astringency and bitterness). Furthermore, phenolic acids and anthocyanins may also influence bitterness and the latter are also responsible for beverages' color. Thus, it is necessary to perform molecular studies to better understand the effect of fining agents in the overall phenolic composition of beverages and the resulting organoleptic changes. The molecular interactions between these three classes of phenolic compounds and a yeast protein extract (YPE), designed as a new fining agent, was studied. The binding affinities were assessed by fluorescence quenching at two temperatures (21 °C and 37 °C) and in two reaction media (water and wine model solution). The size of aggregates formed was characterized by Dynamic Light Scattering and the selectivity of protein interaction was analyzed by electrophoresis. Overall, pentagalloylglucoside (tannin) showed the highest binding affinity for YPE, followed by malvidin 3-glucoside (anthocyanin), p-coumaric acid (phenolic acid) and gallic acid (phenolic acid). The studied temperatures and solvents affected the interaction affinities as well as the aggregates' size. Binding selectivity of proteins from YPE was not found. These results open new perspectives to control the fining process by using the YPE as a fining agent taking into account the further effect in the organoleptic properties of beverages.

Interactions of dietary polyphenols with epithelial lipids: advances from membrane and cell models in the study of polyphenol absorption, transport and delivery to the epithelium.

Currently, diet-related diseases such as diabetes, obesity, hypertension, and cardiovascular diseases account for 70% of all global deaths. To counteract the rising prevalence of non-communicable diseases governments are investing in persuasive educational campaigns toward the ingestion of fresh fruits and vegetables. The intake of dietary polyphenols abundant in Mediterranean and Nordic-type diets holds great potential as nutritional strategies in the management of diet-related diseases. However, the successful implementation of healthy nutritional strategies relies on a pleasant sensory perception in the mouth able to persuade consumers to adopt polyphenol-rich diets and on a deeper understanding on the chemical modifications, that affect not only their chemical properties but also their physical interaction with epithelial lipids and in turn their permeability, location within the lipid bilayer, toxicity and biological activity, and fate during absorption at the gastro-intestinal epithelium, transport in circulation and delivery to the endothelium. In this paper, we review the current knowledge on the interactions between polyphenols and their metabolites with membrane lipids in artificial membranes and epithelial cell models (oral, stomach, gut and endothelium) and the findings from polyphenol-lipid interactions to physiological processes such as oral taste perception, gastrointestinal absorption and endothelial health. Finally, we discuss the limitations and challenges associated with the current experimental approaches in membrane and cell model studies and the potential of polyphenol-rich diets in the quest for personalized nutritional strategies ("personalized nutrition") to assist in the prevention, treatment, and management of non-communicable diseases in an increasingly aged population.

Recent advances in extracting phenolic compounds from food and their use in disease prevention and as cosmetics.

Phenolic compounds in plants are essential components of human nutrition, which provide various health benefits. However, some missing links became the research in phenolic compounds structures and potential applications in a challenging work. Despite universal extraction methods with mixtures of different organic solvents are generally adopted in the analysis of phenolic compounds, a need for establish a specific procedure is still open. The great heterogeneity in food and food by-products matrices and the lack of standardized methods which combine chromatographic with spectrophotometric techniques to calculate the amount of phenolic compounds joined with the absence of specific standards hamper to accurate know the real amount of phenolic compounds. Indeed, the high complexity in nature and chemistry of phenolic compounds clearly difficult to establish a daily intake to obtain certain healthy outcomes. Hence, despite the potential of phenolic compounds to use them in cosmetic and healthy applications have been widely analyzed, some concerns must be considered. The chemical complexity, the interactions between phenolic compounds and other food components and the structural changes induced by food processing joined with the lack in the understanding of phenolic compounds metabolism and bioavailability undergo the need to conduct a comprehensive review of each factors influencing the final activity of phenolic compounds. This paper summarizes the potential of phenolic compounds for disease prevention and cosmetics production, as well as their many other uses derived from their antioxidant activity. This paper illustrates the potential of phenolic compounds for disease prevention and cosmetics production, as well as their many other uses derived from their antioxidant activity.

Bioactive Peptides and Dietary Polyphenols: Two Sides of the Same Coin.

The call for health-promoting nutraceuticals and functional foods containing bioactive compounds is growing. Among the great diversity of functional phytochemicals, polyphenols and, more recently, bioactive peptides have stood out as functional compounds. The amount of an ingested nutrient able to reach the bloodstream and exert the biological activity is a critical factor, and is affected by several factors, such as food components and food processing. This can lead to unclaimed interactions and/or reactions between bioactive compounds, which is particularly important for these bioactive compounds, since some polyphenols are widely known for their ability to interact and/or precipitate proteins/peptides. This review focuses on this important topic, addressing how these interactions could affect molecules digestion, absorption, metabolism and (biological)function. At the end, it is evidenced that further research is needed to understand the true effect of polyphenol-bioactive peptide interactions on overall health outcomes.

Comparison of the in vitro gastrointestinal bioavailability of acylated and non-acylated anthocyanins: Purple-fleshed sweet potato vs red wine.

Acylated anthocyanins from purple-fleshed sweet potato (PFSP) have been reported to have multiple benefits to human health. Although, the bioavailability of these anthocyanins remains unknown. In the present study, a characterization of the gastrointestinal bioavailability of PFSP anthocyanins was assayed and compared with the bioavailability of Red Wine anthocyanins. Acylated anthocyanins showed higher resistance to overall simulated digestions when compared to less complex anthocyanins from Red wine, with degradation at the intestinal level of about 30% and 45%, respectively. Transport rates of absorption of acylated anthocyanins were not dependent on the cell type. However, a higher transport efficiency was observed in gastric cells (8%) when compared to the intestinal cells (5%). Glucose and proteins, but not starch, decreased the transport efficiency of anthocyanins in about 3-7% in gastric cells and 2-3% in intestinal cells. These results bring new insights and lay the groundwork for further research on acylated anthocyanins bioavailability.

A Critical Review of Bioactive Food Components, and of their Functional Mechanisms, Biological Effects and Health Outcomes.

BACKGROUND: Eating behaviours are closely related to some medical conditions potentially leading to death such as cancer, cardiovascular disease and diabetes. Healthy eating practices, maintaining a normal weight, and regular physical activity could prevent up to 80% of coronary heart disease, 90% of type-2 diabetes and onethird of all cancers [1]. METHOD: Over the last two decades, the food industry has invested much effort in research and development of healthier, more nutritious foods. These foods are frequently designated "functional" when they contain nutritional components required for healthy living or "nutraceuticals" when intended to treat or prevent disease or disorders through a variety of bioactive (e.g., antioxidant, antimicrobial, immunomodulatory, hypocholesterolaemic) functions that are performed by functional enzymes, probiotics, prebiotics, fibres, phytosterols, peptides, proteins, isoflavones, saponins or phytic acid, among other substances. RESULTS: Some agricultural and industrial residues have proven to be excellent choices as raw materials for producing bioactive compounds and have been proposed as potentially safe natural sources of antimicrobials and/or antioxidants for the food industry. Functional food ingredients containing bioactive compounds could be used as plant extracts by pharmaceutical and food industries. CONCLUSION: Bioactive food components influence health outcomes.

Wine Flavonoids in Health and Disease Prevention.

Wine, and particularly red wine, is a beverage with a great chemical complexity that is in continuous evolution. Chemically, wine is a hydroalcoholic solution (~78% water) that comprises a wide variety of chemical components, including aldehydes, esters, ketones, lipids, minerals, organic acids, phenolics, soluble proteins, sugars and vitamins. Flavonoids constitute a major group of polyphenolic compounds which are directly associated with the organoleptic and health-promoting properties of red wine. However, due to the insufficient epidemiological and in vivo evidences on this subject, the presence of a high number of variables such as human age, metabolism, the presence of alcohol, the complex wine chemistry, and the wide array of in vivo biological effects of these compounds suggest that only cautious conclusions may be drawn from studies focusing on the direct effect of wine and any specific health issue. Nevertheless, there are several reports on the health protective properties of wine phenolics for several diseases such as cardiovascular diseases, some cancers, obesity, neurodegenerative diseases, diabetes, allergies and osteoporosis. The different interactions that wine flavonoids may have with key biological targets are crucial for some of these health-promoting effects. The interaction between some wine flavonoids and some specific enzymes are one example. The way wine flavonoids may be absorbed and metabolized could interfere with their bioavailability and therefore in their health-promoting effect. Hence, some reports have focused on flavonoids absorption, metabolism, microbiota effect and overall on flavonoids bioavailability. This review summarizes some of these major issues which are directly related to the potential health-promoting effects of wine flavonoids. Reports related to flavonoids and health highlight some relevant scientific information. However, there is still a gap between the knowledge of wine flavonoids bioavailability and their health-promoting effects. More in vivo results as well as studies focused on flavonoid metabolites are still required. Moreover, it is also necessary to better understand how biological interactions (with microbiota and cells, enzymes or general biological systems) could interfere with flavonoid bioavailability.