Fish allergy, mainly caused by Parvalbumin (PV), is a worldwide health issue with few effective mitigation options. This study investigated Maillard conjugation using chitosan (CS) and various saccharides to modify the structural, functional, and allergenic properties of turbot (Scophthalmus maximus) PV. Structural analyses, including SDS-PAGE, Western blotting, FTIR spectroscopy, and Circular dichroism, confirmed successful conjugation and significant changes in secondary structure, including decreases in α-helical content and increases in β-sheet and random-coil fractions. Glycation significantly boosted antioxidant activity, with total phenolic content (TPC) increasing up to 10.3 times and DPPH radical scavenging reaching 74.5% in the CS–xylose–PV conjugate (CXTPV). Indirect ELISA revealed notable (p < 0.05), sugar-dependent reductions in IgE-binding capacity, with reductions of up to approximately 72% for CXTPV. RBL-2H3 cell assays showed decreased β-hexosaminidase release (about 75% reduction), lowered IL-6 secretion, and strong inhibition of IL-4 production, indicating reduced allergenic potential and immune regulation. CXTPV demonstrated the best overall performance. These findings suggest that CS–saccharide Maillard conjugation is an effective approach for creating hypoallergenic marine ingredients with improved bioactive properties.
Allergic rhinitis (AR) is a major global public health issue, with current treatments struggling to balance efficacy and safety, necessitating innovative immunotherapeutic strategies. Artemisia sieversiana (A. sieversiana), a common and potent inhalant allergen, severely impacts patients' quality of life. This study systematically investigates the role of A. sieversiana pollen protein in inducing AR and its potential for establishing immune tolerance. Protein characterization identified four core allergens—Art si 1, Art si 2, Art si 3, and Art si 7—and a specific AR mouse model was successfully established. Subsequently, a dissolvable microneedle was used as a delivery carrier for A. sieversiana protein to intervene in AR mice during the pre-seasonal (PSI) and in-seasonal (ISI) periods. Results showed that incremental micro-needle delivery significantly alleviated AR symptoms, modulated sIgE and sIgG1/sIgG2a balance, promoted regulatory T cell (Treg) differentiation, reduced pro-inflammatory cytokines IL-4, IL-5, IL-13, IL-33, and upregulated IFN-γ. Splenic transcriptomic analysis revealed that PSI can directly suppress IL-17 signaling pathway activation, while ISI modulates immunity through multiple pathways, including protein digestion and oxidative phosphorylation. Furthermore, both interventions downregulated the mRNA and protein expression levels of the key gene Gdf15, facilitating immune tolerance. In conclusion, this study provides novel strategies and theoretical foundations for the immunotherapy of AR caused by Artemisia pollen.
Hydrolyzed infant formulas are widely used in cow’s milk allergy management, yet standardized approaches for evaluating their residual allergenicity remain lacking. We developed an integrated assessment framework combining infant-oriented in vitro gastrointestinal digestion, serum IgE binding, mast cell degranulation, and LC-MS/MS-based peptidomic and epitope analyses. Five commercial hydrolyzed formulas were evaluated using sera from 33 cow’s milk-allergic infants, with three additional products for independent validation. Electrophoretic analysis showed progressive reduction of high-molecular-weight bands with hydrolysis degree; however, IgE-binding and mast cell degranulation assays revealed that several partially hydrolyzed formulas retained substantial allergenic activity, and gastrointestinal digestion could potentiate rather than abolish it. Peptidomic profiling identified 4,790 peptides from 692 proteins; epitope mapping against 236 linear B-cell epitopes linked residual allergenicity more closely to epitope retention and allergen-source composition than to peptide size. Digestion profiling alone proved insufficient, underscoring the need for this multi-dimensional framework in safety evaluation and regulatory decision-making.
Background/Objectives: Food allergy-induced intestinal inflammation can impair lactose digestion and absorption by damaging the epithelium, leading to secondary lactase deficiency with no effective treatments. The immunometabolism nuclear receptor PPAR-γ regulates gut epithelial function and nutrient absorption. This study aimed to determine whether PPAR-γ activation can preserve lactose digestion and absorption during allergic inflammation and to elucidate the underlying mechanisms. Methods: In an ovalbumin-sensitized Brown Norway rat model of food allergy, animals were treated with either the PPAR-γ agonist rosiglitazone or the antagonist GW9662. Lactose absorption was assessed by in vivo lactose tolerance tests (blood glucose monitoring) and intestinal transit measurements. Jejunal tissues were analyzed for lactase gene expression, lactase enzyme activity, and SGLT1/GLUT2 transporter levels. Results: Allergic rats exhibited reduced weight gain, delayed intestinal transit, and lactose malabsorption (lower blood glucose after lactose challenge), accompanied by sharply decreased jejunal lactase mRNA, enzyme activity, and SGLT1/GLUT2 levels. Rosiglitazone treatment restored intestinal PPAR-γ expression and markedly improved lactose absorption, normalizing the lactose tolerance curve. Rosiglitazone also increased lactase gene expression and enzyme activity, and upregulated SGLT1 levels. In contrast, PPAR-γ inhibition with GW9662 further reduced lactase and transporter levels and failed to improve absorption. Conclusions: PPAR-γ signaling maintains intestinal lactose digestive capacity of rats during allergic inflammation by sustaining lactase production and monosaccharide transporter expression. Our findings verify an immunometabolism mechanism linking nuclear receptor activation to enhanced nutrient absorption and highlight PPAR-γ agonism as a promising therapeutic strategy to alleviate food allergy-associated lactose malabsorption.
Background The strain-specific roles of Lachnospiraceae in food allergy (FA) pathogenesis position this family as a promising therapeutic target. However, its pronounced functional heterogeneity and oxygen sensitivity impose significant barriers to functional food development. Scope and approach This review critically synthesizes clinical and experimental evidence correlating altered Lachnospiraceae profiles with FA pathogenesis. We integrate analyses of dietary strategies that orchestrate host immunity via microbial metabolites—principally short-chain fatty acids (SCFAs)—while evaluating delivery platforms and clinical translation pathways for functional food applications. Key findings and conclusions Lachnospiraceae strains exhibit profound functional diversity regarding FA protection. Specific dietary constituents (e.g., resistant starches, polyphenols, and N-acetylneuraminic acid) selectively propagate therapeutically relevant strains. These isolates exert anti-allergic effects via synergistic mechanisms, including the fortification of intestinal barrier integrity and the induction of regulatory T-cell differentiation. However, some effective interventions coincide with a reduction in aggregate Lachnospiraceae abundance, highlighting the divergence between taxonomic load and functional output and necessity for strain-level characterization. To bridge the translational gap, future research must prioritize: (1) establishing causal strain-function linkages through integrated multi-omics and gnotobiotic validation; (2) optimizing metabolic performance via precision synbiotic formulations rather than generic dietary modulation; and (3) developing scalable, biomimetic encapsulation systems to ensure the viability and functional engraftment of these oxygen-sensitive anaerobes. Addressing these challenges will catalyze the development of precision Lachnospiraceae-based functional foods for FA management.
Fish allergy, primarily driven by Parvalbumin (PV), is a global health concern with limited effective mitigation strategies. This study explored Maillard conjugation using chitosan (CS) and various saccharides to modify the structural, functional, and allergenic properties of turbot (Scophthalmus maximus) PV. Structural analyses: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting (WB), Fourier transform infrared (FTIR) spectroscopy, and Circular dichroism (CD) confirmed the successful conjugation and significant alterations in secondary structure, including a loss of α-helical content and an increase in β-sheet/random coil fractions. Glycation markedly enhanced antioxidant activity, with total phenolic content (TPC) increasing up to 10.3-fold and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging reaching 74.5% in the CS-xylose-PV conjugate (CXTPV). Indirect Enzyme-linked immunosorbent assay (ELISA) showed significant (p < 0.05), sugar-dependent reductions in IgE-binding capacity (up to ~72% for CXTPV). Rat basophilic Leukemia-2H3 (RBL-2H3) cell line assays demonstrated suppressed β-hexosaminidase release (~75% reduction), decreased Interleukin-6 (IL-6) secretion, and potent inhibition of Interleukin-4 (IL-4) production, indicating attenuated allergenic potential and immunomodulatory effects. CXTPV exhibited the strongest overall performance. These results highlight CS-saccharide Maillard conjugation as an effective strategy developed for hypoallergenic marine-derived ingredients with enhanced bioactive properties.
Almond-derived peptide fractions (APs) represent a promising yet underexplored class of plant-based bioactive compounds for ulcerative colitis (UC) management. This study investigated the protective effects of APs against dextran sulfate sodium (DSS)-induced colitis in male BALB/c mice using integrated 16S rRNA sequencing and transcriptomic analysis. Mice received low-dose (200 mg/kg) or high-dose (400 mg/kg) APs during 7-day DSS administration. Both doses significantly attenuated body weight loss, disease activity index, colon shortening, and histopathological damage. Compared with the DSS group, low-dose and high-dose APs reduced disease activity index by 65.9% and 52.4%, increased colon length by 30.0% and 26.5%, decreased histopathological scores by 39.6% and 55.1%, and lowered colonic myeloperoxidase activity by 13.9% and 34.1%, respectively. APs also modulated inflammatory cytokines, improved mucus-barrier-related indices, and enhanced continuous ZO-1 localization at epithelial junctions. Additionally, 16S rRNA sequencing indicated that AP treatment was associated with altered genus-level microbiota profiles after DSS exposure, including changes in Ligilactobacillus, Escherichia-Shigella, and Parabacteroides-related taxa. Transcriptomic analysis suggested dose-associated response patterns: low-dose APs were associated with broader immune-related transcriptional changes, whereas high-dose APs were more closely associated with extracellular matrix organization, focal adhesion, and genes enriched in the PI3K-Akt signaling pathway. These findings support the protective effects of APs in DSS-induced acute colitis and suggest potential associations among microbiota alterations, host transcriptional responses, and mucosal repair.
This study aimed to explore the effect of 2′-Fucosyllactose (2′-FL) on the gut health of aged mice. The results revealed that 2′-FL intervention effectively improved the intestinal permeability and reduced the serum diamine oxidase (DAO) level in aged mice (p < 0.05); in addition, 2′-FL increased the IgA level and decreased the IgG level (p < 0.05). Meanwhile, 2′-FL reduced the serum levels of IL-6, IL-1β, TNF-α, and IFN-γ (p < 0.05). Histopathological analysis indicated that 2′-FL successfully reversed intestinal damage in the jejunum and colon. Additionally, 2′-FL increased the expression of the tight-junction proteins ZO-1 and Claudin-1 both at mRNA and protein levels (p < 0.05), and also down-regulated the expression of pro-inflammatory factors (IL-6, IL-1β) (p < 0.05), and decreased aging-related markers P16INK4α and P21Cip1. Furthermore, 16S rRNA results showed that 2′-FL increased the relative abundance of beneficial bacteria in the gut, such as Lachnospiraceae_UCG-006, norank_f__Muribaculaceae and Lachnospiraceae_NK4A136_group. In conclusion, 2′-FL effectively improved the intestinal immune health of the aged mice and provided a theoretical basis for its application as a functional component in the treatment of intestinal diseases.
Sialic acids are crucial for maintaining intestinal homeostasis, but their role in food allergies remains poorly understood. This study investigates the regulatory function of sialic acid (Neu5Ac) in tropomyosin-induced allergic responses, with the aim of identifying potential therapeutic targets. In a C57BL/6N mouse model sensitized with shrimp tropomyosin, Neu5Ac treatment alleviated allergic symptoms, as evidenced by reduced anaphylaxis scores, lower levels of allergen-specific antibodies and Th2 cytokines, enhanced gut microbiota composition, and increased short-chain fatty acid production. To validate these findings, we used the sialyltransferase inhibitor 3Fax-Peracetyl Neu5Ac to inhibit sialylation in both the mouse and CMT93 cell models. Mice with reduced sialylation displayed more severe allergic symptoms, including diarrhea, elevated anaphylaxis scores, increased antibody levels, a Th2-skewed immune response, compromised intestinal barriers, and higher mortality rates. Similarly, in CMT93 cells, sialylation inhibition led to increased secretion of inflammatory markers and greater cellular permeability. These findings underscore the protective effects of Neu5Ac in alleviating food allergies and suggest that enhancing sialylation could provide a novel therapeutic strategy for managing allergic responses.
Studies have been exploring the connection between the intake of vitamins and the development of food allergy, with a particular focus on folic acid (FA). However, the impact of FA supplementation on food allergy remains a subject of debate. In the present study, the anti-allergic properties of FA and its possible mechanism of action were investigated. In a Brown Norway rat food allergy model, we found that FA downregulated the expression of specific antibodies, while influencing the Th1/Th2 balance. Furthermore, FA was found to reduce the release of particulate matter such as histamine and mast cell proteinase. Transcriptomic analysis provided evidence that FA intervention could reverse gene expression changes induced by food allergies. The gene Hsp90, responsible for producing heat shock proteins (HSP), emerged as a potential key gene involved in the process. In vitro RBL-2H3 cell-based assays suggested that FA might affect HSP90 expression through the glucocorticoid receptor (GR), leading to a reduction in effector cell degranulation. Overall, the results of this study indicate that FA has an alleviating effect on food allergies, with high doses of FA exhibiting more pronounced effects. Moreover, FA's impact on HSP90 expression through GR seems to contribute to a decrease in degranulation during the effector phase.
Saccharomyces boulardii (S. boulardii) has attracted widespread attention due to its antimicrobial and anti-inflammatory properties. In this study, we prepared postbiotics from the heat-inactivated cells (HIC) and cell-free supernatant (CFS) of S. boulardii, with the important component L-arginine (Arg) from the metabolic products included as one of the experimental groups. The results showed that in LPS-stimulated Caco-2 cells, HIC, CFS, and Arg protect intestinal epithelial barrier integrity by inhibiting the expression of TNF-α, IL-1β, and IL-6 while enhancing the expression of occludin and ZO-1 proteins. In dextran sulfate sodium (DSS)-induced colitis mice, HIC, CFS, and Arg alleviate symptoms such as weight loss and colonic damage while suppressing the upregulation of pro-inflammatory factors and the downregulation of tight junction proteins. Moreover, these postbiotics help restore the gut microbiota composition and functionality in colitis mice, with potentially superior regulatory effects compared to sulfasalazine (SASP). Overall, HIC and CFS protect the intestinal barrier function and improve DSS-induced colitis, supporting the development of functional food supplements.
Pd@Pt nanozymes are recognized for their extensive specific surface area and enzyme-like catalytic capabilities. However, the role of Pd@Pt nanoparticles in managing metabolic disorders such as diabetes and its related disorders remains poorly understood. This study endeavors to explore the regulatory function of Pd@Pt nanoparticles in metabolic balance, elucidating the associated mechanisms. We demonstrate that Pd@Pt inhibits the production of reactive oxygen species and modulates oxidative stress through its superoxide-dismutase-like enzyme activity in palmitic-acid-induced insulin resistance cell model. Furthermore, Pd@Pt was found to enhance glucose uptake, reduce hyperglycemia, and improve glucose tolerance and insulin sensitivity, attributable to its anti-inflammatory effects. Additionally, the effectiveness of the multifunctional Pd@Pt-based microneedle in expediting the healing of diabetic wounds was confirmed by suppressing key inflammatory signaling pathways. Collectively, our findings highlight the potential of Pd@Pt nanoparticles as powerful anti-inflammatory agents, offering promising therapeutic options for type 2 diabetes and its associated complications.
Approximately 2.5% of the global population experience allergic reactions to seafood, making it one of the most prevalent and life-threatening allergies. Seafood allergy can lead to the disruption of the intestinal barrier, possibly due to aberrant intestinal glycosylation. In this study, the mechanisms underlying seafood allergy were explored through the lens of intestinal glycobiology. Mice were sensitized with tropomyosin, resulting in significant increases in allergy symptom scores, specific antibody and T helper 2 cytokine levels. Intestinal damage was confirmed by histopathology, as well as by assessments and levels of diamine oxidase and claudin-1. Moreover, alterations in glycosylated proteins within the jejunum were analyzed using high-throughput mass spectrometry and the pGlyco3.0 search engine. Precision N-glycoproteomics analysis yielded 2283 glycosylation peptides corresponding to 655 unique glycosylation sites on 399 proteins. Differential expression and enrichment analyses revealed that differentially expressed glycoproteins were significantly enriched in the extracellular matrix (ECM)-receptor interaction pathway and focal adhesion pathway. In conclusion, tropomyosin sensitization leads to intestinal glycome changes, accompanied by remodeling of the intestinal ECM. Our research establishes an essential theoretical basis for targeting the intestinal glycome and ECM remodeling in a precise and fine-tuned manner for the treatment of food allergies.
Loss of pancreatic islet cell mass and function is one of the most important factors in the development of type 2 diabetes mellitus, and hyperglycemia-induced lesions in other organs are also associated with apoptosis or hyperproliferation of the corresponding tissue cells. The Hippo signaling pathway is a key signal in the regulation of cell growth, proliferation and apoptosis, which has been shown to play an important role in the regulation of diabetes mellitus and its complications. Excessive activation of the Hippo signaling pathway under high glucose conditions triggered apoptosis and decreased insulin secretion in pancreatic islet cells, while dysregulation of the Hippo signaling pathway in the cells of other organ tissues led to proliferation or apoptosis and promoted tissue fibrosis, which aggravated the progression of diabetes mellitus and its complications. This article reviews the mechanisms of Hippo signaling, its individual and reciprocal regulation in diabetic pancreatic pathology, and its emerging role in the pathophysiology of diabetic complications. Potential therapeutics for diabetes mellitus that have been shown to target the Hippo signaling pathway are also summarized to provide information for the clinical management of type 2 diabetes mellitus.
Immunosensors have become a rapid, cost-effective, and sensitive tool for food safety detection, with antibodies serving as essential biorecognition components. However, challenges like low specificity, time-consuming preparation, animal dependency, and high costs limit their application. Recent studies highlight strategies for improving antibody performance, including rational hapten design, optimized conjugation techniques, and spacer arm length optimization. Computer-aided molecular modeling can validate designs before the immunization step, ensuring design efficacy. Phage display enables recombinant antibody production, allowing efficient preparation of antibodies from various phage antibody libraries through tailored screening strategies. Additionally, modifications to the ligands and formats used in chromatography can facilitate the development of high-throughput, cost-effective antibody purification methods. This review also offers a comprehensive overview of the type of immunosensors used in food safety, focusing on optical, electrochemical and multi-mode immunosensors. The goal is to offer new insights and approaches to enhance antibody production efficiency and their use in immunosensors.
Allergen-specific immunotherapy (SIT) is a desirable way of therapy for various allergic diseases such as food allergy (FA). However, frequent visits for more than 3 years and potential adverse effects often hinder patient compliance. Recently, many researchers started focusing on microneedles (MNs) as a new method for SIT. In this study, we proposed an implantable MNs system produced by a two-step casting process, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible polyvinyl alcohol (PVA) pedestal. Different from PVA, silk fibroin hydrogel has preferable vaccine release ability in vivo and in vitro. Once MNs are inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min and implant the OVA-loaded silk microneedle tips in dermal layer as a sustained antigen depot, thus inducing long-lasting immune response for at least 2 weeks. After receiving 3 doses of MN-based immunotherapy, the immune response in OVA-sensitized mice was successfully suppressed, with no apparent side effects. Compared to conventional subcutaneous immunotherapy (total dose of 150 g), MN immunotherapy ameliorated systemic anaphylaxis more effectively even at a lower dose (total dose of 30 g), demonstrating the antigen dose-sparing potential of the proposed MNs. Moreover, due to the prolonged release effect of silk-PVA composite MNs, the frequency of immunotherapy can be significantly reduced. To sum up, through prolonged skin exposure to antigen, this implantable designed MN may offer a new therapeutic strategy for FA treatment with significant improvements in efficacy and convenience. Schematic illustration of silk-PVA composite microneedles, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible PVA pedestal. Once inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min. Subsequently, the OVA-loaded silk microneedle tips were implanted in the dermal layer as a sustained antigen depot and induced long-lasting immune response. This MNs-based immunotherapy can significantly modulate the Th1/Th2 imbalance of sensitized mice