Metabolomics identifies phenotypic biomarkers of amino acid metabolism in milk allergy and sensitized tolerance.

BACKGROUND: A substantial proportion of sensitized individuals tolerate suspected foods without developing allergic symptoms; this phenomenon is known as sensitized tolerance. The immunogenic and metabolic features underlying the sensitized-tolerant phenotype remain largely unknown. OBJECTIVE: We aimed to uncover the metabolic signatures associated with clinical milk allergy (MA) and sensitized tolerance using metabolomics. METHODS: We characterized the serum metabolic and immunologic profiles of children with clinical IgE-mediated MA (n = 30) or milk-sensitized tolerance (n = 20) and healthy controls (n = 21). A comparative analysis was performed to identify dysregulated pathways associated with the clinical manifestations of food allergy. We also analyzed specific biomarkers indicative of different sensitization phenotypes in children with MA. The candidate metabolites were validated in an independent quantification cohort (n = 41). RESULTS: Metabolomic profiling confirmed the presence of a distinct metabolic signature that discriminated children with MA from those with milk-sensitized tolerance. Amino acid metabolites generated via arginine, proline, and glutathione metabolism were uniquely altered in children with sensitized tolerance. Arginine depletion and metabolism through the polyamine pathway to fuel glutamate synthesis were closely associated with suppression of clinical symptoms in the presence of allergen-specific IgE. In children with MA, the polysensitized state was characterized by disturbances in tryptophan metabolism. CONCLUSIONS: By combining untargeted metabolomics with targeted validation in an independent quantification cohort, we identified candidate metabolites as phenotypic and diagnostic biomarkers of food allergy. Our results provide insights into the pathologic mechanisms underlying childhood allergy and suggest potential therapeutic targets.

A review of gluten detoxification in wheat for food applications: approaches, mechanisms, and implications.

With the improved knowledge of gluten-related disorders, especially celiac disease (CD), the market of gluten-free food is growing. However, the current gluten-free diet still presents challenges in terms of nutrition, acceptability, and cost due to the absence of gluten. It is important to note that gluten-related allergies or sensitivities have different underlying causes. And individuals with mild non-celiac gluten disorder symptoms may not necessarily require the same gluten-free treatments. Scientists are actively seeking alternative solutions for these consumers. This review delves into the various strategies employed by researchers for detoxifying gluten or modifying its main protein, gliadin, including genetic treatment, transamidation and deamidation, hydrolysis, and microbial treatments. The mechanisms, constraints of these techniques, their current utilization in food items, as well as their implications for gluten-related disorders, are discussed in detail. Although there is still a gap in the application of these methods as alternative solutions in the real market, the summary provided by our review could be beneficial for peers in enriching their basic ideas and developing more applicable solutions for wheat gluten detoxification.

Food-Pollen Cross-Reactivity and its Molecular Diagnosis in China.

PURPOSE OF REVIEW: Plant-derived foods are one of the most common causative sources of food allergy in China, with a significant relationship to pollinosis. This review aims to provide a comprehensive overview of this food-pollen allergy syndrome and its molecular allergen diagnosis to better understand the cross-reactive basis. RECENT FINDINGS: Food-pollen cross-reactivity has been mainly reported in Northern China, Artemisia pollen is the major related inhalant source, followed by tree pollen (Betula), while grass pollen plays a minor role. Pollen allergy is relatively low in Southern China, with allergies to grass pollen being more important than weed and tree pollens. Rosaceae fruits and legume seeds stand out as major related allergenic foods. Non-specific lipid transfer protein (nsLTP) has been found to be the most clinically relevant cross-reacting allergenic component, able to induce severe reactions. PR-10, profilin, defensin, chitinase, and gibberellin-regulated proteins are other important cross-reactive allergen molecules. Artemisia pollen can induce allergenic cross-reactions with a wide range of plant-derived foods in China, and spring tree pollens (Betula) are also important. nsLTP found in both pollen and plant-derived food is considered the most significant allergen in food pollen cross-reactivity. Component-resolved diagnosis with potential allergenic proteins is recommended to improve diagnostic accuracy and predict the potential risk of causing allergic symptoms.

High intestinal isoleucine is a potential risk factor for food allergy by regulating the mTOR/AKT pathway in dendritic cells.

Food allergy is a global food safety problem with a growing prevalence. People in industrial regions are more susceptible to allergy, but the mechanisms behind this are not fully understood. In this study, the probiotic Lactobacillus casei Zhang (LcZ) was administered to allergic individuals and the impact on allergy-related factors were determined. LcZ alleviated allergenic responses, and there was a significant correlation between the intestinal isoleucine content and IgE concentration. Metagenomics results suggest that the metabolism of the gut microbiota is a source of isoleucine. In a mouse model of food allergy, a high isoleucine diet exacerbated allergic responses and increased the activity of allergenic dendritic cell. In a dendritic cell model, a protein array revealed that the mTOR/AKT pathway mediated the function of isoleucine, and molecular docking suggested that Sestrin2 could be the potential receptor. Overall, this study revealed the role of isoleucine in promoting food allergy, elucidated the underlying mechanisms, and suggested that a high intake of isoleucine could be a potential risk factor for food allergy.

Early-life risk factors for food allergy: Dietary and environmental factors revisited.

There appears a steep increase in the prevalence of food allergy worldwide in the past few decades. It is believed that, rather than genetic factors, the recently altered dietary and environmental factors are the driving forces behind the rapid increase of this disease. Accumulating evidence has implied that external exposures that occurred in prenatal and postnatal periods could affect the development of oral tolerance in later life. Understanding the potential risk factors for food allergy would greatly benefit the progress of intervention and therapy. In this review, we present updated knowledge on the dietary and environmental risk factors in early life that have been shown to impact the development of food allergy. These predominantly include dietary habits, microbial exposures, allergen exposure routes, environmental pollutants, and so on. The key evidence, conflicts, and potential research topics of each theory are discussed, and associated interventional strategies to prevent the disease development and ameliorate treatment burden are included. Accumulating evidence has supported the causative role of certain dietary and environmental factors in the establishment of oral tolerance in early life, especially the time of introducing allergenic foods, skin barrier function, and microbial exposures. In addition to certain immunomodulatory factors, increasing interest is raised toward modern dietary patterns, where adequately powered studies are required to identify contributions of those modifiable risk factors. This review broadens our understanding of the connections between diet, environment, and early-life immunity, thus benefiting the progress of intervention and therapy of food allergy.

Inhibitory effect of d-Tryptophan on the spoilage potential of Shewanella baltica and Pseudomonas fluorescens and its potential application in salmon fillet preservation.

In this study, we found the inhibitory effect of d-Tryptophan (d-Trp) on the bacterial growth and spoilage potential of P. fluorescens and S. baltica. The effectiveness of d-Trp in bacterial growth inhibition was highly dependent on environmental NaCl concentrations. The growth/no growth models were developed to clarify the relationship between salt and d-Trp concentrations for optimal growth-inhibitory effect. It showed that higher levels of NaCl (>3.5%) with d-Trp (>15 mM) are required for growth inhibition. The d-Trp treatment combined with NaCl also retarded the psychrotrophic growth and reduced the respiratory active bacteria at low temperature, indicating that the inhibitory effect of d-Trp might be associated with the tolerance to osmotic and cold stress. Furthermore, the treatment d-Trp combined NaCl (artificial seawater) on salmon fillets was investigated. During refrigerated storage, the d-Trp treated salmon fillet either inoculated with S. baltica or P. fluorescen maintained remained a relatively low level of total volatile basic nitrogen (TVBN) (below 30 mg N/100 g during 8-days storage) and delayed increase of low total viable bacteria counts (TVC) with a longer lag phase of 2 days.

Reduction in Allergenicity and Induction of Oral Tolerance of Glycated Tropomyosin from Crab.

Tropomyosin (TM) is an important crustacean (Scylla paramamosain) allergen. This study aimed to assess Maillard-reacted TM (TM-G) induction of allergenic responses with cell and mouse models. We analyzed the difference of sensitization and the ability to induce immune tolerance between TM and TM-G by in vitro and in vivo models, then we compared the relationship between glycation sites of TM-G and epitopes of TM. In the in vitro assay, we discovered that the sensitization of TM-G was lower than TM, and the ability to stimulate mast cell degranulation decreased from 55.07 ± 4.23% to 27.86 ± 3.21%. In the serum of sensitized Balb/c mice, the level of specific IgE produced by TM-G sensitized mice was significantly lower than TM, and the levels of interleukins 4 and interleukins 13 produced by Th2 cells in spleen lymphocytes decreased by 82.35 ± 5.88% and 83.64 ± 9.09%, respectively. In the oral tolerance model, the ratio of Th2/Th1 decreased from 4.05 ± 0.38 to 1.69 ± 0.19. Maillard reaction masked the B cell epitopes of TM and retained some T cell epitopes. Potentially, Maillard reaction products (MRPs) can be used as tolerance inducers for allergen-specific immunotherapy.

Degraded polysaccharides from Porphyra haitanensis: purification, physico-chemical properties, antioxidant and immunomodulatory activities.

To explore effect of the structural properties of porphyra haitanensis polysaccharide on its biological activity, degraded porphyra polysaccharides were separated and purified by Cellulose DEAE-52 and Sephadex G-100 chromatography, obtaining three purified components (P1, P2 and P3). All the three components were sulfate polysaccharides containing the repeating units of → 3) ß-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →, and → 3) ß-D-galactose (1 → 4) α-L-galactose-6-S (1 →, and → 3) 6-O-methyl-ß-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →. The molecular weight of the three fractions was measured to be 300.3, 130.4 and 115.1 kDa, respectively. Their antioxidant activity was investigated by the determination of the free radical scavenging effect and ferric reducing power. It was found that P1, P2 and P3 possessed marked antioxidant activity. It was also found that they appreciably enhanced the proliferation, phagocytic ability and nitric oxide secretion in RAW264.7 cells. Lower molecular weight and higher sulfate content were beneficial to bioactivities of P. haitanensis polysaccharides. Overall, P2 and P3 possess superior immuno-modulatory activity to that of P1 and PHP. Thus, the current work will provide the basis for the better utilization of P. haitanensis to develop the related functional foods.

Dietary protein-phenolic interactions: characterization, biochemical-physiological consequences, and potential food applications.

Dietary proteins and phenolic compounds are commonly co-existing components that readily interact with each other to yield complexes in a wide range of food systems. The formed complexes play a critical role in the physiochemical characteristics of both reacting molecules, thereby impacting nutritional and quality profiles of related products. In this review, we provided the most updated knowledge on dietary protein-phenolic interactions related with food science and human nutrition, including their mechanisms of complexation, analytical technologies, and alterations in the functionality and nutraceutical properties of both reacting partners. Their potential applications in the industries regarding stability during food processing and storage, impacts on product quality, and fabrication of novel delivery systems for liable bioactives were also discussed. The interactions between dietary proteins and phenolics, either via non-covalent or covalent processes, are ubiquitous in food systems and are closely associated with chemical structures of both compounds and the surrounding conditions, mainly temperature, pH, and the presence of phenolic oxidases. Albeit in different ways, such intermolecular associations induced changes in protein conformational structures, which subsequently impacted their techno-functional properties, digestibility, and allergenic potentials; in turn, the bioaccessibility/bioavailability and health-protecting features of interacted phenolics were modified to various extents, as noticed by in vitro and in vivo evidence. Largely depending on the interaction molecules and preparation steps, those influences can be either favorable or unfavorable in different systems and therefore can be tailored to develop food products and nutraceuticals with maximized functionality and quality attributes.

High-throughput sequencing-based characterization of the predominant microbial community associated with characteristic flavor formation in Jinhua Ham.

Our purpose was to investigate the main bacterial microbiota and volatile profiles in the Chinese traditional dry-cured product-Jinhua ham during different processing stages and to analyze the role of the main microbiota in the formation of characteristic flavor. We determined the microbiota of Jinhua ham by using 16 S high throughput sequencing, and found that Staphylococcus constituted the predominant microbiota throughout the flavor formation process. Based on the volatile profiles of Jinhua dry-cured products from 11 different processing via SPME-GC-MS analysis, Aldehydes were the main groups of volatiles, with the most abundant ones being hexanal (13.89%) and nonanal (3.96%). To further investigate the relationship between predominant microbiota and the major volatile compounds in Jinhua ham, we screened and isolated genus Staphylococcus with high protease and lipase activities. The main Staphylococcus isolates, S. saprophyticus (53.4%) and S. equorum (31.0%) are related to the yields of aldehydes by producing hexanal, nonanal, benzaldehyde, and phenylacetaldehyde, indicating their contributions on the formation of characteristic flavor substances in Jinhua ham.

Preventive Effect of Depolymerized Sulfated Galactans from Eucheuma serra on Enterotoxigenic Escherichia coli-Caused Diarrhea via Modulating Intestinal Flora in Mice.

In this work, the preventive effect of depolymerized sulfated polysaccharides from Eucheuma serra (DESP) on bacterial diarrhea by regulating intestinal flora was investigated in vivo. Based on the enterotoxigenic Escherichia coli (ETEC)-infected mouse diarrhea model, DESP at doses ranging from 50 mg/kg to 200 mg/kg alleviated weight loss and decreased the diarrhea rate and diarrhea index. Serological tests showed that the levels of inflammation-related factors were effectively suppressed. Furthermore, the repaired intestinal mucosa was verified by morphology and pathological tissue section observations. Compared with the model group, the richness and diversity of the intestinal flora in the DESP group increased according to the 16S rRNA high-throughput sequencing of the gut microbiota. Specifically, Firmicutes and Actinobacteria increased, and Proteobacteria decreased after DESP administration. At the family level, DESP effectively improved the abundance of Lactobacillaceae, Bifidobacteriaceae, and Lachnospiraceae, while significantly inhibiting the growth of Enterobacteriaceae. Therefore, the antimicrobial diarrhea function of DESP may be related to the regulation of intestinal microbiota.

A tandem GGDEF-EAL domain protein-regulated c-di-GMP signal contributes to spoilage-related activities of Shewanella baltica OS155.

Cyclic diguanylate (c-di-GMP) is a second messenger involved in the regulation of various physiological processes in bacteria. However, its function in spoilage bacteria has not yet been addressed. Here, we studied the function of a tandem GGDEF-EAL domain protein, Sbal_3235, in the spoilage bacterium Shewanella baltica OS155. The deletion of sbal_3235 significantly reduced the c-di-GMP level, biofilm formation, and exopolysaccharide, trimethylamine (TMA), and putrescine production; sbal_3235 deletion also downregulated the expression of the torS and speF genes and affected membrane fatty acid composition. Site-directed mutagenesis in conserved GGDEF and EAL motifs abolished diguanylate cyclase (DGC) and phosphodiesterase (PDE) activity, respectively. These data indicate that Sbal_3235 is an essential contributor to the c-di-GMP pool with bifunctional DGC and PDE activity, which is involved in the biofilm formation and spoilage activity of S. baltica OS155. Our findings expand the biochemical role of c-di-GMP and uncover its link to spoilage activities, providing novel targets for food quality and safety controlling.

Dietary advanced glycation end-products: Perspectives linking food processing with health implications.

Dietary advanced glycation end products (dAGEs) are complex and heterogeneous compounds derived from nonenzymatic glycation reactions during industrial processing and home cooking. There is mounting evidence showing that dAGEs are closely associated with various chronic diseases, where the absorbed dAGEs fuel the biological AGEs pool to exhibit noxious effects on human health. Currently, due to the uncertain bioavailability and rapid renal clearance of dAGEs, the relationship between dAGEs and biological AGEs remains debatable. In this review, we provide the most updated information on dAGEs including their generation in processed foods, analytical and characterization techniques, metabolic fates, interaction with AGE receptors, implications on human health and reducing strategies. Available evidence demonstrating a relevance between dAGEs and food allergy is also included. AGEs are ubiquitous in foods and their contents largely depend on the reactivity of carbonyl and amino groups, along with surrounding condition mainly pH and heating procedures. Once being digested and absorbed into the circulation, two separate pathways can be involved in the deleterious effects of dAGEs: an AGE receptor-dependent way to stimulate cell signals, and an AGE receptor-independent way to dysregulate proteins via forming complexes. Inhibition of AGEs formation during food processing and reduction in the diet are two potent approaches to restrict health-hazardous dAGEs. To elucidate the biological role of dAGEs toward human health, the following significant perspectives are raised: molecular size and complexity of dAGEs; interactions between unabsorbed dAGEs and gut microbiota; and roles played by concomitant compounds in the heat-processed foods.

Fluorescence-based quantitative platform for ultrasensitive food allergen detection: From immunoassays to DNA sensors.

Food allergies are global health issue with an increasing prevalence that affect food safety; hence, food allergen detection, labeling, and management are considered to be important priorities in the food industry. In this critical review, we provide a comprehensive overview of several fluorescence-based platforms based on different biorecognition ligands, such as antibodies, DNA, aptamers, and cells, for food allergen quantification. Traditional analytical methods are generally unsuitable for food manufacturers to accomplish the real-time identification of food allergens in food products. Therefore, it is important to develop simple, rapid, inexpensive, accurate, and sensitive methods to improve user accessibility. A fluorescence-based quantitative platform provides an excellent detection platform for food allergens because of its high sensitivity. This review summarizes the traditional antibody-based fluorescent techniques for food allergen detection, such as the time-resolved fluoroimmunoassay , immunofluorescence imaging, fluorescence enzyme-linked immune sorbent assay, flow injection fluoroimmunoassay, and fluorescence immunosensors. However, these methods suffer from disadvantages such as the significant rate of false-positive and false-negative results due to antibody cross-reactivity with nontarget food components in the complex food matrix and epitope degradation during food processing. Hence, different types of fluorescence-based immunoassays are suitable for standardization and quantification of allergens in fresh foods. In addition, we summarize new fluorescence-based quantitative platforms, including fluorescence genosensors, fluorescence cell sensors, and fluorescence aptamer sensors. With the advantages of high sensitivity and simple operation, fluorescence biosensors will have great potential in the future and could provide portable methods for multiallergen real-time detection in complex food systems.

Yogurt-sourced probiotic bacteria alleviate shrimp tropomyosin-induced allergic mucosal disorders, potentially through microbiota and metabolism modifications.

BACKGROUND: Shrimp tropomyosin (TM) is a major food allergen that may cause serious allergic responses, lactic acid-producing bacteria (LAPB) are believed to alleviate food allergy, but the mechanisms have not been fully clarified. The aim of this work is to investigate the mechanisms of LAPB in ameliorating food allergy-induced intestinal mucosal disorders and to investigate whether or not these disorders occur by the regulation of gut microbiota and metabolism. METHODS: A TM allergy BALB/c mouse model was established, and two LAPB strains, Bifidobacterium longum (Bi) and Bacillus coagulans (Bc), were used for oral treatment in sensitized mice. The allergic mucosal disorders were assessed by histological analysis and ELISAs. Additionally, microbiota and metabolic modifications were determined by 16S rRNA gene amplicon sequencing and GC-TOF-MS, respectively. RESULTS: YSPB administration suppressed TM-induced intestinal mucosal disorders, restored allergenic Th2 cell over-polarization and dysbiosis, and regulated gut arginine and proline metabolism pathways. Statistical analysis suggested the metabolites aspartate and arginine, as well as several commensal flora groups, to be the critical mediators in the process. CONCLUSIONS: These data demonstrated the correlation between allergic mucosal disorder, T cell subtype differentiation, gut microbiota composition and intestinal metabolism especially the arginine and proline metabolism pathways. We also revealed the significant effects of LAPB in ameliorating food allergy and maintaining the mucosal ecosystem. This study confirmed the efficiency of LAPB in relieving food allergy, provided Bi and Bc as the potential treatment approaches, and suggested amino acid metabolism pathways might be the novel targets for potential clinical applications.

Seafood allergen-induced hypersensitivity at the microbiota-mucosal site: Implications for prospective probiotic use in allergic response regulation.

Food allergy is a serious disease worldwide; it can significantly lower the standard of living of affected individuals and may be life-threatening. In particular, hypersensitivity to seafood has been increasing in recent years owing to rising consumption. The mucosal immune system plays a critical role in the onset of seafood allergy and other allergic diseases. Recently, experimental and clinical evidence has shown that probiotics significantly modulate immune responses and thus suppress allergic reactions. Therefore, in this review, we summarized the basic knowledge of seafood allergy, the mucosal immune system, and probiotic activities. We also reviewed the critical immune factors involved in allergic reactions, as well as the potential mechanism and the potential use of probiotics to ameliorate seafood allergy. The elucidation of these topics may help us to develop preventive and therapeutic approaches for seafood allergy and other immune disorders in the future.

Intestinal inflammation modulates expression of the iron-regulating hormone hepcidin depending on erythropoietic activity and the commensal microbiota.

States of chronic inflammation such as inflammatory bowel disease are often associated with dysregulated iron metabolism and the consequent development of an anemia that is caused by maldistribution of iron. Abnormally elevated expression of the hormone hepcidin, the central regulator of systemic iron homeostasis, has been implicated in these abnormalities. However, the mechanisms that regulate hepcidin expression in conditions such as inflammatory bowel disease are not completely understood. To clarify this issue, we studied hepcidin expression in mouse models of colitis. We found that dextran sulfate sodium-induced colitis inhibited hepcidin expression in wild-type mice but upregulated it in IL-10-deficient animals. We identified two mechanisms contributing to this difference. Firstly, erythropoietic activity, as indicated by serum erythropoietin concentrations and splenic erythropoiesis, was higher in the wild-type mice, and pharmacologic inhibition of erythropoiesis prevented colitis-associated hepcidin downregulation in these animals. Secondly, the IL-10 knockout mice had higher expression of multiple inflammatory genes in the liver, including several controlled by STAT3, a key regulator of hepcidin. The results of cohousing and fecal transplantation experiments indicated that the microbiota was involved in modulating the expression of hepcidin and other STAT3-dependent hepatic genes in the context of intestinal inflammation. Our observations thus demonstrate the importance of erythropoietic activity and the microbiota in influencing hepcidin expression during colitis and provide insight into the dysregulated iron homeostasis seen in inflammatory diseases.

Microbial source tracking: a tool for identifying sources of microbial contamination in the food chain.

The ability to trace fecal indicators and food-borne pathogens to the point of origin has major ramifications for food industry, food regulatory agencies, and public health. Such information would enable food producers and processors to better understand sources of contamination and thereby take corrective actions to prevent transmission. Microbial source tracking (MST), which currently is largely focused on determining sources of fecal contamination in waterways, is also providing the scientific community tools for tracking both fecal bacteria and food-borne pathogens contamination in the food chain. Approaches to MST are commonly classified as library-dependent methods (LDMs) or library-independent methods (LIMs). These tools will have widespread applications, including the use for regulatory compliance, pollution remediation, and risk assessment. These tools will reduce the incidence of illness associated with food and water. Our aim in this review is to highlight the use of molecular MST methods in application to understanding the source and transmission of food-borne pathogens. Moreover, the future directions of MST research are also discussed.