Fucoxanthin Prevents the Ovalbumin-Induced Food Allergic Response by Enhancing the Intestinal Epithelial Barrier and Regulating the Intestinal Flora.

This study aimed to determine whether fucoxanthin alleviated ovalbumin (OVA)-induced food allergy (FA) and explored the possible mechanisms. The results indicated that supplementation with fucoxanthin at 10.0-20.0 mg/kg per day for 7 weeks inhibited food anaphylaxis and the production of immunoglobulin (Ig) E, IgG, histamine, and related cytokines while alleviating allergic symptoms in sensitized mice. Fucoxanthin enhanced the intestinal epithelial barrier by up-regulating tight junction (TJ) protein expression and promoting regenerating islet-derived protein III-gamma (RegIIIγ) and secretory IgA (sIgA) secretion. In addition, fucoxanthin induced the secretion of anti-inflammatory factors (interleukin (IL)-10 and transforming growth factor ß (TGF-ß)) by regulatory T (Treg) cells and decreased the pro-inflammatory factor levels (IL-4, tumor necrosis factor-α (TNF-α), IL-17, and IL-1ß), ameliorating intestinal inflammation. Compared with the model group, beneficial bacteria, such as Lactobacillaceae, increased in the intestinal flora, while pathogenic bacteria like Helicobacteraceae, Desulfovibrionaceae, and Streptococcaceae decreased. Therefore, fucoxanthin may effectively prevent FA by enhancing the intestinal epithelial barrier and reshaping the intestinal flora.

Identification of allergens and allergen hydrolysates by proteomics and metabolomics: A comparative study of natural and enzymolytic bee pollen.

Bee pollen as a plant-derived food is consumed as nutritional/functional supplements by humans. But it might confer foodborne allergenicity in susceptible populations, limiting its extensive application. In this study, five potential allergens including profilin, cystatin, prolamin, expansin, and alcohol dehydrogenase in bee pollen derived from Brassica campestris (BP-Bc), were identified through mass spectrometry-based proteomic analysis. Moreover, different types of enzymes (cellulases, pectases, and papains) serve biological roles in pollen wall breaking and expansion, but also promote allergen release and degradation. Proteomic analysis showed that profilin, cystatin, and alcohol dehydrogenase were significantly reduced in BP-Bc following joint treatment with three enzymes. Metabolomic characterization of potential enzymatic hydrolysates of these significantly-decreased allergens was performed, which showed nine major oligopeptides and six amino acids at significantly higher levels in the enzyme-treated BP-Bc. These findings clarified the culprit responsible for bee pollen allergy and the mechanism of enzymatic desensitization for its further development.

Fish allergens of turbot (Scophthalmus maximus) parvalbumin triggers food allergy via inducing maturation of bone marrow derived dendritic cells and driving Th2 immune response.

Aquatic food allergy has become a key food safety problem and therefore it is urgent to study the mechanism of aquatic food allergy. Turbot parvalbumin (PV) is a major marine food allergen that could cause allergic reactions but the cellular and molecular mechanisms remain to be defined. In this study, we used flow cytometry and ELISA, a coupled co-culture system of dendritic cells and T cells, and revealed that PV could promote the maturation of dendritic cells, mainly by inducing bone marrow-derived dendritic cells (BMDCs) to express MHC II and CD86, and promote the cytokines/chemokines IL-6, IFN-γ, IL-23, and IL-12p70, whereas inhibiting TNF-α expression. Our results suggested that murine BMDCs play a crucial role in the effect of PV on the induction of Th2 responses.

Oxytocin suppresses epithelial cell-derived cytokines production and alleviates intestinal inflammation in food allergy.

Food allergy is a growing healthcare problem worldwide, but prophylactic options and regulatory therapies are limited. Oxytocin (OXT), conventionally acknowledged as a hormone, was recently proven to have potent anti-inflammatory and immunomodulatory activities in certain diseases. Here, we reported the novel function and its underlying mechanisms of OXT on food allergy in vivo and in vitro. We showed that the levels of OXT were elevated in ovalbumin (OVA)-allergic mice and patients with food allergy. In HT-29 cells, OXT inhibited the production of the epithelial cell-derived cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33 by suppressing NF-κB signaling, in which ß-arrestin2 participated. These functions of OXT were abolished by oxytocin receptor (OXTR) depletion. Treating OVA-induced BALB/c mice with OXT suppressed TSLP, IL-25 and IL-33 production and attenuated systemic anaphylaxis and intestinal inflammation. OXTR-/- mice showed extreme increases in TSLP, IL-25 and IL-33 levels as well as severe systemic anaphylaxis and intestinal inflammation. In conclusion, through OXTRs, OXT has a promising antiallergic effect on experimental food allergy by suppressing epithelial TSLP, IL-25 and IL-33 production via inhibiting NF-κB signaling and upregulating ß-arrestin2 expression. Our study provides a new therapeutic perspective for food allergy in humans.

Short-Chain Fatty Acids Calibrate RARα Activity Regulating Food Sensitization.

Gut-microbiota dysbiosis links to allergic diseases. The mechanism of the exacerbation of food allergy caused by gut-microbiota dysbiosis remains unknown. Regulation of retinoic acid receptor alpha (RARα) signaling is critical for gut immune homeostasis. Here we clarified that RARα in dendritic cells (DCs) promotes Th2 cell differentiation. Antibiotics treatment stimulates retinoic acid signaling in mucosal DCs. We found microbiota metabolites short-chain fatty acids (SCFAs) maintain IGF-1 levels in serum and mesenteric lymph nodes. The IGF-1/Akt pathway is essential for regulating the transcription of genes targeted by RARα. And RARα in DCs affects type I interferon (IFN-I) responses through regulating transcription of IFN-α. Our study identifies SCFAs crosstalk with RARα in dendritic cells as a critical modulator that plays a core role in promoting Th2 cells differentiation at a state of modified/disturbed microbiome.

Immunomodulatory Response of Toll-like Receptor Ligand-Peptide Conjugates in Food Allergy.

Covalent conjugation of allergens to toll-like receptor (TLR) agonists appears to be a powerful strategy for the development of safety compounds for allergen-specific immunomodulatory response toward tolerance in allergy. In this work, we have synthesized two family of ligands, an 8-oxoadenine derivative as a ligand for TLR7 and a pyrimido[5,4-b]indole as a ligand for TLR4, both conjugated with a T-cell peptide of Pru p 3 allergen, the lipid transfer protein (LTP) responsible for LTP-dependent food allergy. These conjugates interact with dendritic cells, inducing their specific maturation, T-cell proliferation, and cytokine production in peach allergic patients. Moreover, they increased the Treg-cell frequencies in these patients and could induce the IL-10 production. These outcomes were remarkable in the case of the TLR7 ligand conjugated with Pru p 3, opening the door for the potential application of these allergen-adjuvant systems in food allergy immunotherapy.

IL-27 as a potential biomarker for distinguishing between necrotising enterocolitis and highly suspected early-onset food protein-induced enterocolitis syndrome with abdominal gas signs.

BACKGROUND: The initial clinical manifestations and abdominal imaging findings of neonates with necrotising enterocolitis (NEC) and food protein-induced enterocolitis syndrome (FPIES) are sometimes similar; however, their prognosis and therapies are different. We aimed to evaluate the utility of interleukin (IL)-27 as a differentiation marker between NEC and highly suspected early onset (HSEO)-FPIES. METHODS: All samples used in this study were obtained from the neonatal diagnosis centre of Children's Hospital of Chongqing Medical University. In the case-control study, neonates with NEC (n = 13), HSEO-FPIES (n = 9), and jaundice (control, n = 8) were enroled to determine the serum IL-27 levels using commercial enzyme-linked immunosorbent assay (ELISA) kits. In the validation cohort study, the NEC (n = 87), HSEO-FPIES (n = 62), and jaundice (control, n = 54) groups were included to analyse the diagnostic efficiency of IL-27 for discriminating between NEC and HSEO-FPIES using a receiver operating characteristic (ROC) curve. FINDINGS: In the case-control study, IL-27 levels were higher in the NEC group than in the HSEO-FPIES group (p = 0·005). In the cohort study, the area under the ROC curve (AUC) of IL-27 for differentiating NEC from HSEO-FPIES was 0·878, which was higher than the AUCs of IL-6 (0·761), C-reactive protein (0·800), white blood cell count (0·637), neutrophils (0·765), lymphocytes (0·782), neutrophil to lymphocyte ratio (0·781), and platelet count (0·729). INTERPRETATION: Serum IL-27 is a novel biomarker that may potentially discriminate NEC from HSEO-FPIES in neonates. FUNDING: None.

A new approach for activation of the kiwifruit cysteine protease for usage in in-vitro testing.

Actinidin (Act d 1), a highly abundant cysteine protease from kiwifruit, is one of the major contributors to the development of kiwifruit allergy. Many studies have focused on the optimization of Act d 1 purification and its role in the development of food allergies. Testing on cell culture monolayers is a common step in the elucidation of food allergen sensitization. In the case of cysteine proteases, an additional activation step with L-cysteine is required before the testing. Hence, we aimed to evaluate whether L-cysteine already present in commonly used cell culture media would suffice for Act d 1 activation. Successfully activated Act d 1 (98.1% of proteolytic activity, as compared to L-cysteine activated Act d 1) was further tested in two commonly used 2D model systems (Caco-2 and HEK293 cells) to evaluate its role on the mRNA expression of cytokines involved in the innate immunity (IL-1ß, IL-6, TNFα, TSLP). Furthermore, the contribution of Act d 1 in the promotion of inflammation through regulation of inducible nitric oxide synthase (iNOS) mRNA expression was also examined. These results demonstrate that activation of cysteine proteases can be achieved without previous enzyme incubation in L-cysteine -containing solution. Act d 1 incubated in cell culture medium was able to modulate gene expression of pro-inflammatory cytokines when tested on two model systems of the epithelial barrier.

Effects of a Low Dose of T-2 Toxin on the Percentage of T and B Lymphocytes and Cytokine Secretion in the Porcine Ileal Wall.

Plant materials used in the production of pig feed are frequently contaminated with mycotoxins. T-2 toxin is a secondary metabolite of selected Fusarium species, and it can exert a harmful influence on living organisms. Most mycotoxins enter the body via the gastrointestinal tract, and they can modulate the gut-associated lymphoid tissue (GALT) function. However, little is known about the influence of low T-2 toxin doses on GALT. Therefore, the aim of this study was to evaluate the effect of T-2 toxin administered at 50% of the lowest-observed-adverse-effect level (LOAEL) on the percentage of CD2+ T cells, CD4+ T helper cells, CD8+ cytotoxic T cells, CD4+CD8+ double-positive T cells, TCRγδ+ cells, CD5+CD8- B1 cells, and CD21+ B2 cells, and the secretion of proinflammatory (IFN-γ, IL-1ß, IL-2, IL-12/23p40, IL-17A), anti-inflammatory, and regulatory (IL-4, IL-10, TGF-ß) cytokines in the porcine ileal wall. The results of the study revealed that T-2 toxin disrupts the development of tolerance to food antigens by enhancing the secretion of proinflammatory and regulatory cytokines and decreasing the production of anti-inflammatory TGF-ß. T-2 toxin triggered the cellular response, which was manifested by an increase in the percentage of CD8+ T cells and a decrease in the percentage of B2 and Tγδ lymphocytes.

Suppression of Hippo Pathway by Food Allergen Exacerbates Intestinal Epithelia Instability and Facilitates Hypersensitivity.

SCOPE: Hippo signaling is a crucial pathway in innate immune responses, but the relationship between food allergy and Hippo pathway is unknown. The aim of this work is to investigate the regulation of food allergy by Hippo pathway and reveal the molecular mechanisms. METHODS AND RESULTS: Two food allergens tropomyosin and ovalbumin are used to challenge a mouse model and CMT93 intestinal epithelia cell model. The allergic responses and the activation of Hippo pathway are tested in these models. In the mouse model, both allergens trigged significant allergic responses, and Hippo pathway is suppressed after allergen challenge. In CMT93, both allergens upregulate the expression of allergic cytokines thymic stromal lymphopoietin, interleukin (IL)-25, and IL-33. In TAZ KD CMT93, the Hippo pathway is blocked, and the expression of allergenic cytokines are also suppressed. CONCLUSIONS: Both in vivo and in vitro data demonstrate that the two food allergens suppressed Hippo pathway by downregulating TAZ expression, resulting in intestinal epithelia instability, and finally leading to hypersensitivity reactions. These findings provide potential therapeutic targets and molecular markers for food allergy, and provide dietary guidelines for allergenic individuals.

Dysregulation of intestinal epithelial CFTR-dependent Cl- ion transport and paracellular barrier function drives gastrointestinal symptoms of food-induced anaphylaxis in mice.

Food-triggered anaphylaxis can encompass a variety of systemic and intestinal symptoms. Murine-based and clinical studies have revealed a role for histamine and H1R and H2R-pathway in the systemic response; however, the molecular processes that regulate the gastrointestinal (GI) response are not as well defined. In the present study, by utilizing an IgE-mast cell (MC)-dependent experimental model of oral antigen-induced anaphylaxis, we define the intestinal epithelial response during a food-induced anaphylactic reaction. We show that oral allergen-challenge stimulates a rapid dysregulation of intestinal epithelial transcellular and paracellular transport that was associated with the development of secretory diarrhea. Allergen-challenge induced (1) a rapid intestinal epithelial Cftr-dependent Cl- secretory response and (2) paracellular macromolecular leak that was associated with modification in epithelial intercellular junction proteins claudin-1, 2, 3 and 5, E-cadherin and desmosomal cadherins. OVA-induced Cftr-dependent Cl- secretion and junctional protein degradation was rapid occurring and was sustained for 72 h following allergen-challenge. Blockade of both the proteolytic activity and Cl- secretory response was required to alleviate intestinal symptoms of food-induced anaphylaxis. Collectively, these data suggest that the GI symptom of food-induced anaphylactic reaction, secretory diarrhea, is a consequence of CFTR-dependent Cl- secretion and proteolytic activity.

B cells and the microbiota: a missing connection in food allergy.

Food allergies are a major public health concern due to their widespread and rising prevalence. The increase in food allergy is partially due to Western lifestyle habits which deplete protective commensal microbiota. These microbial perturbations can result in adverse host-microbe interactions, altering the phenotype of various immune cells and instigating allergic sensitization. Although B cells are critical to allergic pathology, microbial influences on B cells have been somewhat overlooked. Here, we focus on direct and indirect interactions between bacteria and B cells and how such interactions regulate B-cell phenotype, namely antibody production (IgA, IgE, IgG1, and IgG4) and regulatory B-cell (Breg) function. Understanding how microbes modulate B-cell activity in the context of food allergies is critical to both tracing the development of disease and assessing future treatment options.

Perturbations to Homeostasis in Experimental Models Revealed Innate Pathways Driving Food Allergy.

While type 2 immunity has been conventionally viewed as beneficial against helminths, venoms, and poisons, and harmful in allergy, contemporary research has uncovered its critical role in the maintenance of homeostasis. The initiation of a type 2 immune response involves an intricate crosstalk between structural and immune cells. Structural cells react to physical and chemical tissue perturbations by secreting alarmins, which signal the innate immune system to restore homeostasis. This pathway acts autonomously in the context of sterile injury and in the presence of foreign antigen initiates an adaptive Th2 response that is beneficial in the context of venoms, toxins, and helminths, but not food allergens. The investigation of the triggers and mechanisms underlying food allergic sensitization in humans is elusive because sensitization is a silent process. Therefore, the central construct driving food allergy modeling is based on introducing perturbations of tissue homeostasis along with an allergen which will result in an immunological and clinical phenotype that is consistent with that observed in humans. The collective evidence from multiple models has revealed the pre-eminent role of innate cells and molecules in the elicitation of allergic sensitization. We posit that, with the expanding use of technologies capable of producing formidable datasets, models of food allergy will continue to have an indispensable role to delineate mechanisms and establish causal relationships.

Beyond IgE: Alternative Mast Cell Activation Across Different Disease States.

Mast cells are often regarded through the lens of IgE-dependent reactions as a cell specialized only for anti-parasitic and type I hypersensitive responses. However, recently many researchers have begun to appreciate the expansive repertoire of stimuli that mast cells can respond to. After the characterization of the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis of mast cell activation-a pathway that is independent of the adaptive immune system-researchers are revisiting other stimuli to induce mast cell activation and/or subsequent degranulation independent of IgE. This discovery also underscores that mast cells act as important mediators in maintaining body wide homeostasis, especially through barrier defense, and can thus be the source of disease as well. Particularly in the gut, inflammatory bowel diseases (Crohn's disease, ulcerative colitis, etc.) are characterized with enhanced mast cell activity in the context of autoimmune disease. Mast cells show phenotypic differences based on tissue residency, which could manifest as different receptor expression profiles, allowing for unique mast cell responses (both IgE and non-IgE mediated) across varying tissues as well. This variety in receptor expression suggests mast cells respond differently, such as in the gut where immunosuppressive IL-10 stimulates the development of food allergy or in the lungs where transforming growth factor-ß1 (TGF-ß1) can enhance mast cell IL-6 production. Such differences in receptor expression illustrate the truly diverse effector capabilities of mast cells, and careful consideration must be given toward the phenotype of mast cells observed in vitro. Given mast cells' ubiquitous tissue presence and their capability to respond to a broad spectrum of non-IgE stimuli, it is expected that mast cells may also contribute to the progression of autoimmune disorders and other disease states such as metastatic cancer through promoting chronic inflammation in the local tissue microenvironment and ultimately polarizing toward a unique Th17 immune response. Furthermore, these interconnected, atypical activation pathways may crosstalk with IgE-mediated signaling differently across disorders such as parasitism, food allergies, and autoimmune disorders of the gut. In this review, we summarize recent research into familiar and novel pathways of mast cells activation and draw connections to clinical human disease.

Boiling down the cysteine-stabilized LTP fold - loss of structural and immunological integrity of allergenic Art v 3 and Pru p 3 as a consequence of irreversible lanthionine formation.

BACKGROUND: Non-specific lipid transfer proteins (LTPs) are important allergens in fruits, pollen, vegetables, nuts and latex. Due to their compact structure, LTPs are highly resistant to heat treatment. Here, Art v 3 from mugwort pollen and Pru p 3 from peach were used as model allergens to in-depth investigate structural and immunological properties upon thermal treatment at different buffer conditions. METHODS: Recombinant Art v 3 and Pru p 3 were purified from E. coli and incubated at 95 °C up to 120 min using sodium phosphate buffer pH 3.4 or 7.3. Physicochemical properties of allergens were analyzed in circular dichroism spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering, size exclusion chromatography, and mass spectrometry. The crystal structure of Art v 3.0201 was determined to 1.9 Šresolution. IgG and IgE binding was investigated in ELISA using murine and LTP allergic patients' sera. RESULTS: Highly pure and homogenous recombinant allergens were obtained from bacterial production. The crystal structure of Art v 3.0201 revealed an antiparallel four helix bundle with a C-terminal extension mediating an asymmetric, transient dimer interface and differently sized cavities. Both allergens showed high thermal stability at acidic conditions. In contrast, extensive heat treatment in neutral buffer induced irreversible structural changes due to lanthionine-based cysteine rearrangement. This fostered loss of the typical α-helical structure, increased molecular size and abrogation of IgG and IgE binding epitopes. Pru p 3 lost its structural integrity at shorter heat stress duration than Art v 3, which did however only partially affect the molecule's IgE binding epitopes. CONCLUSION: During thermal treatment, susceptibility to structural changes of the LTP-fold is highly dependent on the surrounding environment but also on intrinsic features of individual LTPs. This is a crucial fact to consider when processing LTP-containing food or food products as this will directly influence their allergenic potential.

Regulating Bcl2L12 expression in mast cells inhibits food allergy.

Rationale: Mast cells play a crucial role in allergic diseases. Yet, the regulation of mast cell bioactivities is not fully understood. This study aims to elucidate the role of B cell lymphoma 2 like protein 12 (Bcl2L12), one of the anti-apoptosis proteins, in regulating mast cell apoptosis. Methods: A food allergy (FA) mouse model was developed to establish mast cell over population in the intestinal tissue. Either compound 48/80 (C48/80) or specific antigens were used to activate mast cells in the intestinal mucosa. Results: After treating with C48/80, apoptosis was induced in mast cells of the intestine of naive control mice, but not in FA mice. The expression of Fas ligand (FasL) was lower in the mast cells of FA mice. Interleukin (IL)-5 was responsible for the suppression of FasL by upregulating the expression of Bcl2L12 in mast cells. Bcl2L12 prevented c-Myc, the major transcription factor of FasL, from binding the FasL promoter to inhibit the expression of FasL in mast cells. Inhibition of Bcl2L12 restored the apoptosis machinery of mast cells in the FA mouse intestine. Conclusions: The apoptosis machinery in mast cells is impaired in an allergic environment. Inhibition of Bcl2L12 restores the apoptosis machinery in mast cells in the FA mouse intestine.

IL-13-induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis.

BACKGROUND: Food-induced anaphylaxis (FIA) is an IgE-dependent immune response that can affect multiple organs and lead to life-threatening complications. The processes by which food allergens cross the mucosal surface and are delivered to the subepithelial immune compartment to promote the clinical manifestations associated with food-triggered anaphylaxis are largely unexplored. OBJECTIVE: We sought to define the processes involved in the translocation of food allergens across the mucosal epithelial surface to the subepithelial immune compartment in FIA. METHODS: Two-photon confocal and immunofluorescence microscopy was used to visualize and trace food allergen passage in a murine model of FIA. A human colon cancer cell line, RNA silencing, and pharmacologic approaches were used to identify the molecular regulation of intestinal epithelial allergen uptake and translocation. Human intestinal organoid transplants were used to demonstrate the conservation of these molecular processes in human tissues. RESULTS: Food allergens are sampled by using small intestine (SI) epithelial secretory cells (termed secretory antigen passages [SAPs]) that are localized to the SI villous and crypt region. SAPs channel food allergens to lamina propria mucosal mast cells through an IL-13-CD38-cyclic adenosine diphosphate ribose (cADPR)-dependent process. Blockade of IL-13-induced CD38/cADPR-dependent SAP antigen passaging in mice inhibited induction of clinical manifestations of FIA. IL-13-CD38-cADPR-dependent SAP sampling of food allergens was conserved in human intestinal organoids. CONCLUSION: We identify that SAPs are a mechanism by which food allergens are channeled across the SI epithelium mediated by the IL-13/CD38/cADPR pathway, regulate the onset of FIA reactions, and are conserved in human intestine.

Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E.

BACKGROUND & AIMS: Confocal laser endomicroscopy (CLE) is a technique that permits real-time detection and quantification of changes in intestinal tissues and cells, including increases in intraepithelial lymphocytes and fluid extravasation through epithelial leaks. Using CLE analysis of patients with irritable bowel syndrome (IBS), we found that more than half have responses to specific food components. Exclusion of the defined food led to long-term symptom relief. We used the results of CLE to detect reactions to food in a larger patient population and analyzed duodenal biopsy samples and fluid from patients to investigate mechanisms of these reactions. METHODS: In a prospective study, 155 patients with IBS received 4 challenges with each of 4 common food components via the endoscope, followed by CLE, at a tertiary medical center. Classical food allergies were excluded by negative results from immunoglobulin E serology analysis and skin tests for common food antigens. Duodenal biopsy samples and fluid were collected 2 weeks before and immediately after CLE and were analyzed by histology, immunohistochemistry, reverse transcription polymerase chain reaction, and immunoblots. Results from patients who had a response to food during CLE (CLE+) were compared with results from patients who did not have a reaction during CLE (CLE-) or healthy individuals (controls). RESULTS: Of the 108 patients who completed the study, 76 were CLE+ (70%), and 46 of these (61%) reacted to wheat. CLE+ patients had a 4-fold increase in prevalence of atopic disorders compared with controls (P = .001). Numbers of intraepithelial lymphocytes were significantly higher in duodenal biopsy samples from CLE+ vs CLE- patients or controls (P = .001). Expression of claudin-2 increased from crypt to villus tip (P < .001) and was up-regulated in CLE+ patients compared with CLE- patients or controls (P = .023). Levels of occludin were lower in duodenal biopsy samples from CLE+ patients vs controls (P = .022) and were lowest in villus tips (P < .001). Levels of messenger RNAs encoding inflammatory cytokines were unchanged in duodenal tissues after CLE challenge, but eosinophil degranulation increased, and levels of eosinophilic cationic protein were higher in duodenal fluid from CLE+ patients than controls (P = .03). CONCLUSIONS: In a CLE analysis of patients with IBS, we found that more than 50% of patients could have nonclassical food allergy, with immediate disruption of the intestinal barrier upon exposure to food antigens. Duodenal tissues from patients with responses to food components during CLE had immediate increases in expression of claudin-2 and decreases in occludin. CLE+ patients also had increased eosinophil degranulation, indicating an atypical food allergy characterized by eosinophil activation.

Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy.

BACKGROUND: The vagus nerve has emerged as an important modulator of the intestinal immune system. Its anti-inflammatory properties have been previously shown in innate and Th1/Th17 predominant inflammatory models. To what extent the vagus nerve is of importance in Th2 inflammatory responses like food allergy is still unclear. In this study, we therefore aimed to investigate the effect of vagotomy (VGX) and vagus nerve stimulation (VNS), on the development and severity of experimental food allergy. METHODS: Balb/C mice were first sensitized with ovalbumin (OVA) in the presence of alum. Prior to oral challenges with OVA, mice were subjected to VGX or VNS. Disease severity was determined by assessing severity and onset of diarrhoea, OVA-specific antibody production, mast cell number and activity, inflammatory gene expression in duodenal tissue and lamina propria immune cells by flow cytometry analysis. RESULTS: When compared to control mice, VGX did not significantly affect the development and severity of the disease in our model of food allergy. VNS, on the other hand, resulted in a significant amelioration of the different inflammatory parameters assessed. This effect was independent of α7nAChR and is possibly mediated through the dampening of mast cells and increased phagocytosis of OVA by CX3CR1hi macrophages. CONCLUSIONS: These results underscore the anti-inflammatory properties of the vagus nerve and the potential of neuro-immune interactions in the intestine. Further insight into the underlying mechanisms could ultimately lead to novel therapeutic approaches in the treatment of not only food allergy but also other immune-mediated diseases.