Integrating Widely Targeted Lipidomics and Transcriptomics Unravels Aberrant Lipid Metabolism and Identifies Potential Biomarkers of Food Allergies in Rats.

SCOPE: Oral food challenges (OFCs) are currently the gold standard for determining the clinical reactivity of food allergy (FA) but are time-consuming, expensive, and risky. To screen novel peripheral biomarkers of FA and characterize the aberrant lipid metabolism in serum, 24 rats are divided into four groups: peanut, milk, and shrimp allergy (PA, MA, and SA, respectively) and control groups, with six rats in each group, and used for widely targeted lipidomics and transcriptomics analysis. METHODS AND RESULTS: Widely targeted lipidomics reveal 144, 162, and 206 differentially accumulated lipids in PA, MA, and SA groups, respectively. The study integrates widely targeted lipidomics and transcriptomics and identifies abnormal lipid metabolism correlated with widespread differential accumulation of diverse lipids (including triacylglycerol, diacylglycerol, sphingolipid, and glycerophospholipid) in PA, MA, and SA. Simplified random forest classifier is constructed through five repetitions of 10-fold cross-validation to distinguish allergy from control. A subset of 15 lipids as potential biomarkers allows for more reliable and more accurate prediction of FA. Independent replication validates the reproducibility of potential biomarkers. CONCLUSION: The results reveal the major abnormalities in lipid metabolism and suggest the potential role of lipids as novel molecular signatures for FA.

Contribution of five major apple polyphenols in reducing peanut protein sensitization and alleviating allergencitiy of peanut by changing allergen structure.

Peanuts are prone to trigger allergic reactions with high mortality rate. There is currently no effective way to prevent peanut allergy. In order to reduce the allergy risk of peanuts, it's significant to reduce sensitization of peanut prior to ingestion. In this study, the effects of five major apple polyphenols (epicatechin, phlorizin, rutin, chlorogenic acid, and catechin) -peanut protein on the sensitization of peanut allergens were studied by BALB/c peanut allergy model to access the contribution of each polyphenol in apple to peanut allergen sensitization reduction. Then, the mechanism was explored in terms of the effect of polyphenols on the simulated gastric digestion of peanut protein and the changes in structure of Ara h 1. The results showed that polyphenol binding could alleviate allergencitiy of peanut and regulate MAPK related signaling pathway. Among the five major apple polyphenols, epicatechin had the strongest inhibitory effect. The binding of epicatechin to the constitutive epitopes arginine led to changes in the spatial structure of Ara h 1, which resulted in the effective linear epitopes reduction. Modification of peanut allergens with polyphenols could effectively reduce the sensitization of peanut protein.

Effect of Fortified Inoculation with Indigenous Lactobacillus brevis on Solid-State Fermentation of Light-Flavor Baijiu.

Baijiu, one of the world's oldest distilled liquors, is widely consumed globally and has gained increasing popularity in East Asia. However, a comprehensive understanding of the underlying principles behind this traditional liquor product remains elusive. Currently, Baijiu is facing the industrial challenge of modernization and standardization, particularly in terms of food quality, safety, and sustainability. The current study selected a Lactobacillus brevis strain based on experiments conducted to assess its environmental tolerance, enzyme activity, and fermentation performance, and highlight its exceptional fermentation characteristics. The subsequent analysis focused on examining the effects of fortifying the fermentation process of L.brevis on key microbiotas, physicochemical parameters, and volatile profiles. The qPCR results revealed that the inoculated L. brevis strategically influenced the the composition of the dominant microbial communities by promoting mutual exclusion, ultimately leading to improved controllability of the fermentation process. Moreover, the metabolism of the inoculated L. brevis provided more compounds for the formation of flavor profiles during fermentation (the content of ethyl acetate was increased to 57.76 mg/kg), leading to a reduction in fermentation time (from 28 d to 21 d). These findings indicate promising potential for the application of the indigenous strain in Baijiu production.

Long Non-Coding RNAs Expressed in the Peanut Allergy for Understanding the Pathophysiology of Peanut Allergy Rat Model.

BACKGROUND: Peanut allergy (PA) has become a clinical and public health problem, which is mainly regulated by genetics, immune responses, and environmental factors. Diagnosis and treatment for PA have always remained huge challenges due to its multiple triggers. Studies have shown that long non-coding RNAs (lncRNAs) play a critical role in the development of allergic diseases. METHOD AND RESULTS: In the current study, we examined the plasma lncRNA expression profiles of peanut allergy Brown Norway rats and healthy controls and 496 differently expressed lncRNAs were identified, including 411 up-regulated genes and 85 down-regulated genes. We screened 8 lncRNAs based on the candidate principle and the candidates were verified in individual samples by quantitative real-time PCR. Then, the four lncRNA-based diagnostic model was established by least absolute shrinkage and selection operator (LASSO) and logistic regression, which was proved by area under the receiver operating characteristic curve (AUC). CONCLUSIONS: In summary, we assessed the correlation between lncRNA expression levels and the diagnosis of peanut allergy, which may perform a vital role in guiding the management of peanut allergy.

Chlorogenic acid improves food allergy through the AMPK/ACC/CPT-1 pathway.

Chlorogenic acid (CGA) is a polyphenol prevalent in daily food and plants. Food allergy (FA) can lead to metabolic disorders of the immune system. The objective of this study was to investigate CGA therapeutic effect on FA and regulatory mechanism through shrimp food allergy in mice models. Here, 24 female BALB/C mice were randomly allocated into the (I) Control group, (II) Food allergy group, (III) Chlorogenic acid low (50 mg/kg), and (IV) high group (200 mg/kg). Enzyme-linked immunosorbent assay revealed that CGA decreased levels of IgE and IgG induced by food allergy significantly. Real-time PCR demonstrated that high-dose chlorogenic acid significantly reduced Acetyl-CoA carboxylase (ACC) mRNA expression and increased Carnitine palmitoyltransferase-1 (CPT-1) mRNA expression. Western blot indicated that CGA promoted a noticeable increase at the levels of AMP-activated protein kinase (AMPK) and ACC phosphorylation, resulting in a significant activation in AMPK and inhibition in ACC, and increased CPT-1 expression. Consequently, CGA improves FA by the regulation of the AMPK/ACC/CPT-1 signaling pathway in the spleen. PRACTICAL APPLICATIONS: Chlorogenic acid is a water-soluble polyphenolic substance that is widely distributed in natural plants that show a variety of pharmacological effects. At present, CGA has been developed as a weigh-reducing tonic in western countries. As one of the most widely found and most easily obtained phenolic acids from food, the diverse physiological effects of CGA (such as anti-inflammatory, antioxidant, metabolic regulation, intestinal microbial regulation, etc.) imply its potential for application in functional foods, food additives, and clinical medicine. However, the basic molecular mechanisms of its effects have not been elucidated. In this study, CGA reduced allergy in a mouse model, likely by interacting with the AMPK/ACC/CPT-1 pathway.

Sialic acid and food allergies: The link between nutrition and immunology.

Food allergies (FA), a major public health problem recognized by the World Health Organization, affect an estimated 3%-10% of adults and 8% of children worldwide. However, effective treatments for FA are still lacking. Recent advances in glycoimmunology have demonstrated the great potential of sialic acids (SAs) in the treatment of FA. SAs are a group of nine-carbon α-ketoacids usually linked to glycoproteins and glycolipids as terminal glycans. They play an essential role in modulating immune responses and may be an effective target for FA intervention. As exogenous food components, sialylated polysaccharides have anti-FA effects. In contrast, as endogenous components, SAs on immunoglobulin E and immune cell surfaces contribute to the pathogenesis of FA. Given the lack of comprehensive information on the effects of SAs on FA, we reviewed the roles of endogenous and exogenous SAs in the pathogenesis and treatment of FA. In addition, we considered the structure-function relationship of SAs to provide a theoretical basis for the development of SA-based FA treatments.

Peanut allergen induces more serious allergic reactions than other allergens involving MAPK signaling pathways.

There is no universally accepted uniform research to classify the severity of allergic reactions triggered by different food allergens. We established a food allergy model based on repeated intragastric administrations of proteins from peanut, egg, milk, or soybean mixed with cholera toxin followed by oral food challenges with a high dose of the sensitizing proteins. Increased specific IgE, specific IgG1, allergic symptom scores, histamine, murine mast cell proteases-1, vascular leakage, Th2 cytokines, and mast cell infiltration in the lungs and intestine were found in the allergic groups via enzyme-linked immunosorbent assay, hematoxylin-eosin, and toluidine blue staining. Each sensitized group showed a decrease in body temperature and Th1 cytokines after oral food challenge. The increased levels of Th2 cytokines, IL-25, IL-33, and TSLP, and related asthma genes ARG1, DCN, LTB4R1 and NFKBIA as well as the activation of MAPK signaling pathways were also revealed by quantitative real-time PCR and western blotting. In terms of the severity of food allergies, peanut allergy was the most serious followed by egg and milk, and soybean allergy was the least severe. Compared to other allergic groups, asthma genes were regulated through the MAPK signaling pathways to produce related Th2 cytokines in peanut allergy; consequently, mice in the peanut group exhibited more severe allergic reactions. Comparison of the severity of food allergies is required for the development of milder prevention for severe food allergies.

Widely Targeted Lipidomics and Transcriptomics Analysis Revealed Changes of Lipid Metabolism in Spleen Dendritic Cells in Shrimp Allergy.

Shrimp allergy (SA) is pathological type 2 inflammatory immune responses against harmless shrimp protein allergen, which is caused by complex interactions between dendritic cells (DCs) and other immune cells. Lipid metabolism in different DCs states are significantly changed. However, the lipid metabolism of spleen DCs in SA remain ambiguous. In this study, we established a BALB/c mouse shrimp protein extract-induced allergy model to determine the lipid profile of spleen DCs in SA, and the molecular mechanism between lipid metabolism and immune inflammation was preliminarily studied. Spleen DCs were sorted by fluorescence-activated cell sorting, and then widely targeted lipidomics and transcriptomics analysis were performed. Principal component analysis presented the lipidome alterations in SA. The transcriptomic data showed that Prkcg was involved in lipid metabolism, immune system, and inflammatory signaling pathway. In the correlation analysis, the results suggested that Prkcg was positively correlated with triacylglycerol (Pearson correlation coefficient = 0.917, p = 0.01). The lipidomics and transcriptomics integrated pathway analysis indicated the activated metabolic conversion from triacylglycerol to 1,2-diacyl-sn-glycerol and the transmission of lipid metabolism to immune inflammation (from triacylglycerol and ceramide to Prkcg) in SA spleen DCs, and cellular experiments in vitro showed that glyceryl trioleate and C16 ceramide treatment induced immune function alteration in DCs.

High-Fat Diet-Induced Obesity Aggravates Food Allergy by Intestinal Barrier Destruction and Inflammation.

INTRODUCTION: The increase in high-fat diet (HFD)-induced obesity and food allergy leads to an assumption that the 2 are related. This study aims to (1) systematic verification of HFD-induced obesity aggravates food allergy and (2) explore the correlation and molecular mechanisms of HFD-induced obesity promotes food allergy. METHODS: Female BALB/c mice are divided into the control group (control), the ovalbumin (OVA)-sensitized group (OVA), the HFD-induced obesity group (HFD), and HFD-induced allergic obesity group (HFD + OVA). RESULTS: In vivo data showed that HFD feed enhance clinical symptoms and intestinal mucosa villi shed on allergic mice. Moreover, we found that HFD and OVA irritation enhanced levels of mast cell degranulation and Th2 humoral response. Additionally, Western blot analysis showed the potentiation of peroxisome proliferator-activated receptor γ (PPAR γ) remarkably reduced on intestinal in HFD and OVA group, thereby inhibiting the expression of nuclear factor kappa B (NF-κB)/PPAR γ signal the phosphorylation of NF-κB P65. CONCLUSIONS: Overall, our results suggest that HFD-induced obesity is a potential risk factor for food allergy, which related to intestinal barrier destruction and inflammation through the PPAR γ/NF-κB signaling pathway.

Effects of Fatty Acid Oxidation and Its Regulation on Dendritic Cell-Mediated Immune Responses in Allergies: An Immunometabolism Perspective.

Type 1 allergies, involve a complex interaction between dendritic cells and other immune cells, are pathological type 2 inflammatory immune responses against harmless allergens. Activated dendritic cells undergo extensive phenotypic and functional changes to exert their functions. The activation, differentiation, proliferation, migration, and mounting of effector reactions require metabolic reprogramming. Dendritic cells are important upstream mediators of allergic responses and are therefore an important effector of allergies. Hence, a better understanding of the underlying metabolic mechanisms of functional changes that promote allergic responses of dendritic cells could improve the prevention and treatment of allergies. Metabolic changes related to dendritic cell activation have been extensively studied. This review briefly outlines the basis of fatty acid oxidation and its association with dendritic cell immune responses. The relationship between immune metabolism and effector function of dendritic cells related to allergic diseases can better explain the induction and maintenance of allergic responses. Further investigations are warranted to improve our understanding of disease pathology and enable new treatment strategies.

Gender differences in food allergy depend on the PPAR γ/NF-κB in the intestines of mice.

AIMS: Epidemiology shows that gender affects the incidence of food allergy. However, there is a lack of evidence of gender differences in food allergies and little is known about the mechanisms. The aim of this study was to excavate potential reasons for gender differences in food allergy based on estrogen. MAIN METHODS: Female and male BALB/c mice sensitized with ovalbumin (OVA) were established to analyze the difference in food allergy. The systemic anaphylactic, including OVA-specific IgE, OVA-specific IgG, histamine, and cytokines, was assessed using an enzyme-linked immunosorbent assay (ELISA). ELISA also detected the estradiol in serum. Western blotting and immunofluorescence were used to detect the estrogen receptor. Peroxisome proliferator-activated receptor gamma (PPARγ) implicated in immune homeostasis and nuclear factor kappa-B (NF-κB) were determined by western blotting. Immunohistochemistry and hematoxylin-eosin (H&E) staining were used to detect zonula occludens-1 (ZO-1), tryptase, forkhead box protein P3 (Foxp3), and intestinal morphology, respectively. KEY FINDINGS: Female mice were more vulnerable to food allergy. Female mice treated with OVA did exhibit more serious systemic anaphylaxis than male mice. We observed increased levels of estradiol in serum, estrogen receptor, NF-κB, and decreased levels of PPAR γ in female mice. Furthermore, the intestinal mucosal integrity and intestinal permeability were more impaired in female mice treated with OVA than male mice. SIGNIFICANCE: Clarify the mechanism of gender differences in food allergies can provide targets in female mice and provide personalized diagnosis, management, and treatment of food allergy for female mice.

Cholera toxin induces food allergy through Th2 cell differentiation which is unaffected by Jagged2.

AIMS: Cholera toxin is often used to induce food allergies. However, its exact mode of action and effect remain ambiguous. In this study, we established a BALB/c mouse cholera toxin/ovalbumin-induced food allergy model to determine the molecular basis and signaling mechanisms of the immune regulation of cholera toxin during food allergy. MATERIALS AND METHODS: The adjuvant activity of cholera toxin was analyzed by establishing mouse allergy model, and the allergic reaction of each group of mice was evaluated. The effect of cholera toxin on Th1/Th2 cell differentiation was analyzed to further explore the role of cholera toxin in allergen immune response. We stimulated bone marrow-derived dendritic cells (BMDCs) with cholera toxin in vitro to investigate the effect of cholera toxin on Notch ligand expression. BMDCs and naive CD4+T cells were co-cultured in vitro, and their cytokine levels were examined to investigate whether cholera toxin regulates Th cell differentiation via the Jagged2 Notch signaling pathway. KEY FINDINGS: The results showed that in the presence of allergens, cholera toxin promotes Th2 cell differentiation and enhances the body's immune response. Cholera toxin induces expression of the Notch ligand Jagged2, but Jagged2 Notch signaling pathway is not required to promote BMDCs-mediated differentiation of Th2 cells. SIGNIFICANCE: This study initially revealed the mechanism by which cholera toxin plays an adjuvant role in food allergy, and provides reference for future related research.