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Background: Eosinophilic esophagitis (EoE) predominantly affects males across all ages; however, little is known about sex differences for other aspects of EoE., Objective: To investigate associations between sex and clinical presentation, endoscopic features, treatment choice and response in EoE patients in real-world practice., Methods: Cross-sectional analysis of the multicenter EoE CONNECT registry. The independent contribution of patients' sex and other relevant variables were statistically assessed by multivariate models., Results: A total of 2976 patients (76% male) were evaluated. Males were diagnosed at a younger age compared to females (32.7 ± 14.8 vs. 34.8 ± 15.6 years, respectively; p = 0.002) with similar diagnostic delay. EoE symptoms varied significantly between sexes, with food impaction predominating in males and dysphagia, heartburn, regurgitation and abdominal and epigastric pain in females. However, female sex contributed to higher symptom severity at diagnosis as measured with Dysphagia Symptom Score (R 2  = 0.57; p = 0.013) and presented higher peak eosinophil count in esophageal biopsies (p = 0.005). Males showed increased risk of stricturing or mixed phenotypes (adjusted OR 1.43, 95%CI:1.05-1.96; p = 0.024). No association was found between patients' sex and first-line treatment modality: proton pump inhibitors (PPI) were preferred over topical corticosteroids in patients with inflammatory phenotypes instead of stricturing or mixed phenotypes, and in patients who did not present food impaction. Both topical corticosteroids and dietary interventions were preferred over PPI in pediatric patients regardless of sex., Conclusions: Sex is associated with clinical and phenotypical presentation of EoE at diagnosis, with more fibrotic findings in males but higher symptom score in females., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Abstract Background The Paediatric Eosinophilic Oesophagitis Module (PedsQL-EoE) was developed in English as a valid and reliable questionnaire to assess health-related quality of life (HRQoL) in children with EoE. The aim of this study was to evaluate the validity and reliability of the PedsQL-EoE that was previously adapted to Spanish by our group. Methods This cross-sectional multicentre study was conducted in 36 paediatric gastroenterology units. Groups with and without dietary restrictions were studied separately. The PedsQL-EoE consists of 33 items divided into seven factors. Age-specific versions of the PedsQL-EoE were sent by e-mail to children and parents. Statistical analysis was used to study the questionnaire structure by means of exploratory factor analysis and interitem correlations. Confirmatory factor analysis (CFA) was applied to verify the proposed model as well as its psychometric properties through SMSR (standardized root mean square), outer loadings and R-square. To study construct validity and reliability, Cronbach´s alpha coefficient, convergent validity (AVE), discriminant validity (HTMT) and intraclass correlation coefficients (ICC) were used. Results A total of 341 children and 394 parents participated with 307 matched answers. The median age was 12 years, and 75% were male. The questionnaire structure explained 68% and 66% of the total variance for parents and children, respectively. Five items showed negative correlations and were removed from the questionnaire. CFA applied to the new model supported the following construct: SMRS was less than 0.08, outer loadings measured above 0.5, and R2 explained more than 89% of the total variance. Once the modifications were performed, good internal consistency was demonstrated, with Cronbach’s alpha values > 0.7, AVE values > 0.5 and HTMT

Eosinophilic esophagitis and IgE-mediated food allergy are both food-triggered diseases that are increasing in prevalence. They share many clinical links, including significant comorbidity and similar food triggers, and as atopic diseases, they likely share upstream mechanisms related to barrier function and signals leading to T H 2 skewing. In this review, we focus on links between eosinophilic esophagitis and IgE-mediated food allergy with an emphasis on what insights may be derived from overlapping food triggers and immune phenotypes. Through further investigation of these connections, we may be able to better understand not only IgE-mediated food allergy and eosinophilic esophagitis but also general atopic response to food proteins and evolution of allergic response to food. [ABSTRACT FROM AUTHOR]

Background: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses., Objective: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice., Methods: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations., Results: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness., Conclusion: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Eosinophilic esophagitis (EoE) is a common cause of swallowing difficulties in both children and adults. The incidence of EoE has been increasing over the past decades, which cannot be solely attributed to improved diagnostic techniques. EoE is more common in adults than in children. The diagnosis is confirmed by a biopsy from the esophageal mucosa showing a significant infiltration of eosinophils. Many patients respond to treatment with proton pump inhibitors, but those with severe EoE may require dietary modifications, topical steroids, and/or dilation of esophageal strictures. This review covers the incidence, risk factors, natural course, diagnosis, and treatment options for EoE, both within the Icelandic healthcare system andi n a broader context.

Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID) based on the involved gastrointestinal segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including its pathogenesis, diagnosis, treatment, and prognosis. Additionally, details regarding 28 cases of non-EoE-EGID recently diagnosed at our Japanese tertial medical center are presented and compared with 20 EoE cases diagnosed during the same period at the same medical center. Comparisons of the two groups clarified differences regarding age- and gender-dependent prevalence between the two conditions, and also showed that systemic involvement and disease severity were greater in the non-EoE-EGID patients. Notably, diagnosis of non-EoE-EGID is difficult because of its lack of specific or characteristic symptoms and endoscopic findings. The clinical characteristics of EoE and non-EoE-EGID differ in many ways, while they also share several genetic, clinical, laboratory, and histopathological features. [ABSTRACT FROM AUTHOR]

Eotaxin-3 is a key chemokine with a relevant role in eosinophilic esophagitis, a rare chronic immune/antigen-mediated inflammatory disorder. Eotaxin-3 is a potent activator of eosinophil emergence and migration, which may lead to allergic airway inflammation. We investigated, using bioinformatics tools, the protein structure and the possible effects of the known variations reported in public databases. Following a procedure already established, we created a 3D model of the whole protein and modeled the structure of 105 protein variants due to known point mutations. The effects of the amino acid substitution at the level of impact on protein structure, stability, and possibly function were detected by the bioinformatics procedure and described in detail. A web application was implemented to browse the results of the analysis and visualize the 3D models, with the opportunity of downloading the models and analyzing them using their own software. Among 105 amino acid substitutions investigated, the study evidenced in 44 cases at least one change in any of the investigated structural parameters. Other six variations are also relevant, although a structural effect was not detected by our analysis, because they affected amino acids highly conserved, which suggests a possible function role. All these variations should be the object of particular attention, as they may induce a loss of functionality in the protein.

Celiac disease (CeD) and eosinophilic esophagitis (EoE) are immune-mediated disorders that can occur in the same patient. A retrospective study at a tertiary care hospital was conducted to determine the prevalence of EoE in a pediatric population with CeD and to compare characteristics of patients with both diseases to patients with CeD-only. Among the 148 patients with CeD identified in the study, 11 patients had both CeD and EoE (7.4%). Patients with both CeD and EoE had a higher absolute eosinophil count (per μL) at diagnosis compared to patients with CeD-only (454.1 ± 122.7 vs 231.9 ± 19.4, P =.003). In conclusion, there was a higher proportion of EoE in patients with CeD than would be expected in the general population, suggesting a potential pathophysiological overlap between the 2 diseases. An elevated peripheral absolute eosinophil count may help predict which patients with CeD may additionally have EoE. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic oesophagitis (EoE) is an immune-mediated oesophageal disorder causing dysphagia. Patients with EoE experience reduced QoL due to symptoms; however, this has not been assessed in the New Zealand population. The aim of this study was to assess QoL in patients with EoE in New Zealand. Methods: This observational study recruited participants from two New Zealand hospitals. Records were reviewed to confirm diagnoses, and consenting participants completed an electronic survey, consisting of the Dysphagia Symptom Questionnaire (DSQ) score and the QoL-specific EoE (EoE-QoL-A) questionnaire score. Correlation analysis examined the relationship between the DSQ and EoE-QoL-A scores. Differences in baseline variables were assessed. Univariate logistic regression assessed the association of variables with disease activity and QoL. Results: Fifty-four participants responded, and four were excluded due to incomplete surveys. The majority (76%) were male, and the median age was 47 years (IQR 42–58). The median DSQ was 49 (IQR 0–60), and the median EoE-QoL-A score was 68 (IQR 48–80). A reduced EoE-QoL-A score was associated with active disease (OR = 0.96,95% CI 0.926–0.995). Significant associations were found between disease activity and overall EoE-QoL-A score (r = −0.37, p < 0.01) as well as the sub-categories eating and diet (r = −0.54, p < 0.001), social (r = 0.30, p < 0.05), and emotional impact (r = −0.44, p < 0.01). The EOE-QoL-A score was higher in those on PPI (75 vs. 60, p = 0.02). Conclusion: This study identified a decreased quality of life (QoL) in individuals with EoE in New Zealand, aligning with international literature. The increased DSQ scores suggest a possible gap in current management approaches. The correlation between the DSQ and QoL highlights the need for improved care models of care for EoE. [ABSTRACT FROM AUTHOR]

A subset of patients with eosinophilic esophagitis (EoE) respond to proton-pump inhibitor (PPI) therapy, however they cannot be distinguished prior to PPI trial and the mechanism of PPI response remains unclear. Improved understanding of the distinct patient phenotypes in PPI-responsive EoE (PPI-r-EoE), PPI-non-responsive EoE (PPI-nr-EoE) and erosive esophagitis (EE) may help guide management. The aim of this paper is to compare the clinical and allergy profiles of PPI-r-EoE versus PPI-nr-EoE and EE. This was a retrospective case-control study of EoE patients (>15 eos/hpf on esophageal biopsies) at a tertiary center. EE controls were identified from the pathology database. EoE patients were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response to twice-daily PPI for ≥8 weeks. Patient demographics, comorbidities, symptoms, allergy history and endoscopic findings were recorded. Univariate analyses were performed using the Fisher-exact test or t -test. Multivariable analyses were performed using logistic regression. In all, 104 EoE (57 PPI-r-EoE/47 PPI-nr-EoE) and 80 EE subjects were included. On multivariable analyses, allergic conditions (aOR 20.1, P  < 0.0001) and rings (aOR 108.3, P  = 0.001) were independent predictors for PPI-r-EoE versus EE, whereas allergic conditions (aOR 4.8, P  = 0.03), rings (aOR 27.5, P  = 0.002) and furrows (aOR 17.1, P  = 0.04) were independent predictors for PPI-nr-EoE versus EE. Esophageal rings was the only significant predictor found in PPI-nr-EoE versus PPI-r-EoE (OR 2.5, P  = 0.03). Allergic conditions and esophageal rings are significantly more prevalent in PPI-r-EoE and PPI-nr-EoE compared with EE. PPI-r-EoE appears clinically similar to PPI-nr-EoE and significantly different from EE. Further studies are needed to delineate the underlying pathophysiology of PPI-r-EoE versus PPI-nr-EoE. [ABSTRACT FROM AUTHOR]

Direct comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce. To compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages. Cross-sectional analysis of the EoE CONNECT registry. The adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood‐onset cohort (patients diagnosed at <18 y), 254. Vomiting, nausea, chest and abdominal pain, weight loss, slow eating and food aversion were significantly more frequent in children; dysphagia, food bolus impaction and heartburn predominated in adults. A family history of EoE was present in 16% of pediatric and 8.2% of adult patients (p <0.001). Concomitant atopic diseases did not vary across ages. Median±IQR diagnostic delay (years) from symptom onset was higher in adults (2.7 ± 6.1) than in children (1 ± 2.1; p <0.001). Esophageal strictures and rings predominated in adults (p <0.001), who underwent esophageal dilation more commonly (p = 0.011). Inflammatory EoE phenotypes were more common in children (p = 0.001), who also presented higher eosinophil counts in biopsies (p = 0.015) and EREFS scores (p = 0.017). Despite PPI predominating as initial therapy in all cohorts, dietary therapy and swallowed topical corticosteroids were more frequently prescribed in children (p <0.001). Childhood‐onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment. [ABSTRACT FROM AUTHOR]

BackgroundEosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers.MethodsBlood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE.ResultsFrench children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets.ConclusionsOur study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort.

Simple Summary: Eosinophilic esophagitis is a chronic disease that can be complicated by fibrosis and strictures in the esophagus. Fibroblasts are a cell type that are considered important mediators of this process. The aim of this study was to better understand how fibroblasts can cause strictures by using publicly available single-cell RNA sequencing data to identify the different types of fibroblasts in patients with eosinophilic esophagitis. We identified at least two types of fibroblasts in eosinophilic esophagitis. Our analysis shows that fibroblasts are important contributors to the communication that occurs between cells in the human esophagus and that each of the fibroblast types has a unique way of interacting with other cell types (e.g., with epithelial cells or immune cells). This work can be used to provide additional insights into how strictures form in eosinophilic esophagitis. Fibroblast heterogeneity remains undefined in eosinophilic esophagitis (EoE), an allergic inflammatory disorder complicated by fibrosis. We utilized publicly available single-cell RNA sequencing data (GSE201153) of EoE esophageal biopsies to identify fibroblast sub-populations, related transcriptomes, disease status-specific pathways and cell–cell interactions. IL13-treated fibroblast cultures were used to model active disease. At least 2 fibroblast populations were identified, F_A and F_B. Several genes including ACTA2 were more enriched in F_A. F_B percentage was greater than F_A and epithelial–mesenchymal transition upregulated in F_B vs. F_A in active and remission EoE. Epithelial–mesenchymal transition was also upregulated in F_B in active vs. remission EoE and TNF-α signaling via NFKB was downregulated in F_A. IL-13 treatment upregulated ECM-related genes more profoundly in ACTA2− fibroblasts than ACTA2+ myofibroblasts. After proliferating epithelial cells, F_B and F_A contributed most to cell–cell communication networks. ECM–Receptor interaction strength was stronger than secreted or cell–cell contact signaling in active vs. remission EoE and significant ligand–receptor pairs were driven mostly by F_B. This unbiased analysis identifies at least 2 fibroblast sub-populations in EoE in vivo, distinguished in part by ACTA2. Fibroblasts play a critical role in cell–cell interactions in EoE, most profoundly via ECM–receptor signaling via the F_B sub-group. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an emerging chronic T helper type 2 (Th2)-associated, allergic, and immune-mediated disease, characterized histologically by eosinophil-predominant mucosal inflammation and clinically by esophageal dysfunction. Over the past years, the prevalence of EoE has dramatically increased globally. Until recently, most studies of EoE focused on using human biopsies, which are also used for diagnostic purposes, or esophageal epithelial cell lines, which led to major advances in the understanding of EoE. Despite this, a robust mouse model that mimics human disease is still crucial for both understanding disease pathogenesis and as a preclinical model for testing future therapeutics. Herein, we describe a highly reproducible and robust model of EoE that can be performed using wild-type mice by ear sensitization with oxazolone (OXA) followed by intraesophageal challenges. Experimental EoE elicited by OXA mimics the main histopathological features of human EoE, including intraepithelial eosinophilia, epithelial and lamina propria thickening, basal cell hyperplasia, and fibrosis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of EoE in mice using oxazolone Support Protocol 1: Preparing the mouse esophagus for histological analysis Support Protocol 2: Assessment of epithelial and lamina propria thickness using H&E staining Support Protocol 3: Assessment of eosinophilic infiltration using anti-MBP and basal cell proliferation using anti-Ki-67 staining Support Protocol 4: Flow cytometry of mouse esophageal samples Support Protocol 5: ELISA on protein lysates of esophageal samples., (© 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID) based on the involved gastrointestinal segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including its pathogenesis, diagnosis, treatment, and prognosis. Additionally, details regarding 28 cases of non-EoE-EGID recently diagnosed at our Japanese tertial medical center are presented and compared with 20 EoE cases diagnosed during the same period at the same medical center. Comparisons of the two groups clarified differences regarding age- and gender-dependent prevalence between the two conditions, and also showed that systemic involvement and disease severity were greater in the non-EoE-EGID patients. Notably, diagnosis of non-EoE-EGID is difficult because of its lack of specific or characteristic symptoms and endoscopic findings. The clinical characteristics of EoE and non-EoE-EGID differ in many ways, while they also share several genetic, clinical, laboratory, and histopathological features.

Introduction: There is a complex interrelationship between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) potentially promoting the occurrence and modulating severity of each other reciprocally. Presence of Barrett's esophagus (BE) is a defining factor for the diagnosis of GERD. While several studies investigated the potential impact of concomitant GERD on the presentation and course of EoE, little was known with regards to BE in EoE patients. Methods: We analyzed prospectively collected clinical, endoscopic, and histological data from patients enrolled in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) regarding differences between EoE patients with (EoE/BE+) versus without BE (EoE/BE−) and determined the prevalence of BE in EoE patients. Results: Among a total of 509 EoE patients included in our analysis, 24 (4.7%) had concomitant BE with a high male preponderance (EoE/BE+ 83.3% vs. EoE/BE− 74.4%). While there were no differences in dysphagia, odynophagia was significantly (12.5 vs. 3.1%, p = 0.047) more common in EoE/BE+ versus EoE/BE−. General well-being at last follow-up was significantly lower in EoE/BE+. Endoscopically, we observed an increased incidence of fixed rings in the proximal esophagus in EoE/BE+ (70.8 vs. 46.3% in EoE/BE−, p = 0.019) and a higher fraction of patients with a severe fibrosis in the proximal histological specimen (8.7 vs. 1.6% in EoE/BE, p = 0.017). Conclusion: Our study reveals that BE is twice as frequent in EoE patients compared to general population. Despite many similarities between EoE patients with and without BE, the finding of a more pronounced remodeling in EoE patients with Barrett is noteworthy. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical corticosteroids (STC) or prior inadequate response, intolerance or contraindication to STC., Design: Pre-specified analysis of data from the phase 3 LIBERTY EoE TREET study on patients who received dupilumab 300 mg once a week or placebo for 24 weeks (W24) in parts A and B, and an additional 28 weeks (W52) in part C. Patients were categorised as with/without prior STC use and with/without inadequate/intolerance/contraindication to STC. The proportion of patients achieving ≤6 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score and Histologic Scoring System grade/stage scores were assessed for each subgroup., Results: Regardless of prior STC use, dupilumab increased the proportion of patients achieving ≤6 eos/hpf and improved DSQ score versus placebo at W24, with improvements maintained or improved at W52. The DSQ score and the proportion of patients achieving ≤6 eos/hpf after switching from placebo to dupilumab at W24 were similar to those observed in the dupilumab group at W24, regardless of prior STC use or inadequate/intolerance/contraindication to STC. Improvements in other outcomes with dupilumab were similar in patients with/without prior STC use or inadequate/intolerance/contraindication to STC., Conclusion: Dupilumab 300 mg once a week demonstrated efficacy and was well tolerated in patients with EoE regardless of prior STC use or inadequate response, intolerance and/or contraindication to STC., Trial Registration Number: NCT03633617., Competing Interests: Competing interests: AJB: Dr Falk Pharma, Norgine, Nutricia, Sanofi, SST and Thelial—research funding; Alimentiv, Aqilion, AstraZeneca, Dr Falk Pharma, Laborie, Medtronic, Regeneron Pharmaceuticals and Sanofi—consulting fees. ED: Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Celgene/Receptos/BMS, GSK, Meritage, Miraca, Nutricia, Regeneron Pharmaceuticals, Revolo and Shire/Takeda—research funding; Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, Gossamer Bio, GSK, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron Pharmaceuticals, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE and Upstream Bio—consulting fees; Allakos, Holoclara and Invea—educational funding. IH: Allakos, AstraZeneca, Calyx/Parexel, Eli Lilly, Ellodi/Adare, EsoCap, Gossamer Bio, Nexstone, Pfizer/Arena, Phathom, Receptos/BMS, Sanofi/Regeneron Pharmaceuticals and Shire/Takeda—consulting fees; Allakos, AstraZeneca, Ellodi/Adare, Pfizer/Arena, Receptos/BMS, Regeneron Pharmaceuticals and Shire/Takeda—research funding; Sanofi/Regeneron Pharmaceuticals—speaker fees. AJL: Dr Falk Pharma and EsoCap—consulting fees; Dr Falk Pharma, Ellodi and Regeneron Pharmaceuticals—research funding. CS: Adare Pharmaceuticals, AstraZeneca, Calypso, EsoCap, Dr Falk Pharma, GmbH and Regeneron Pharmaceuticals—consulting fees. AS, EM, JM and XS: employees of Regeneron Pharmaceuticals and may hold stock and/or stock options in the company. EL, LG and LM: employees of Sanofi and may hold stock and/or stock options in the company., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Eosinophilic esophagitis (EoE) is an antigen-mediated chronic inflammatory disease of the esophagus, the prevalence of which has steadily increased in recent years. The pathogenesis of EoE is not yet well-defined; however, recent studies have demonstrated that the esophageal microbiota is an essential regulator of physiological and pathological processes of EoE. Currently, research on EoE and microbiota is an emerging field of study that is receiving increasing attention. Here, we review existing EoE-related esophageal microbiota studies to explore the potential mechanisms underlying esophageal microbiota-mediated EoE. The esophageal microbiome is altered in patients with EoE. Although α diversity is usually not significantly different, an increase in Haemophilus and a decrease in Firmicutes were observed in EoE patients. The role of microbiota in initiating and perpetuating inflammation is not fully understood. Current evidence suggests that the penetration of microbiota leads to the activation of epithelial cells as well as innate and adaptive immune cells, with the subsequent release of cytokines, leading to immune responses and inflammation. The involvement of toll-like receptors in EoE also supports the potential role of the microbiota in the progression of this disease. While EoEinduced inflammation can also lead to alterations in the local microbiome. Moreover, dietary modifications, proton pump inhibitors, and corticosteroids can modulate the esophageal microbiota; however, definitive conclusions about the alterations of microbes after treatment cannot be drawn. These findings provide promising avenues for future studies. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers. Methods: Blood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE. Results: French children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets. Conclusions: Our study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort. [ABSTRACT FROM AUTHOR]

Introduction: High levels of serum food‐specific IgG4 (sIgG4) have been reported in patients with EoE. The objective of this study was to examine whether serum sIgG4 levels to foods and aeroallergens are higher in EoE patients than allergic controls and to investigate the association between sIgG4 and EoE clinical characteristics. Methods: This was a case–control study nested in a prospective EoE Cohort. EoE cases were defined per consensus guidelines, and controls were individuals with symptoms who were confirmed to be EoE‐negative on upper endoscopy. Demographic and clinical information was prospectively collected. Serum IgE and sIgG4 were measured to foods and aeroallergens by ImmunoCAP. Mean levels of sIgG4 were compared between cases and controls, and logistic regression models were used to examine predictors of elevated milk sIgG4 levels. Results: The analysis included 123 individuals (EoE n = 93, control n = 30) with a similar distribution of allergic disease between EoE patients and controls (86% vs. 93%; p =.30). EoE patients had significantly higher sIgG4 levels to all allergens evaluated, with the exception of birch (p =.24). Milk sIgG4 levels were independently associated with milk consumption (OR 4.95; p =.01) and the presence of sIgE to milk (OR 4.23; p =.008). Conclusion: Serum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non‐EoE controls, and higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Whether sIgG4 plays a pathogenic role in EoE or could be used as an EoE biomarker remains unknown and warrants further study. [ABSTRACT FROM AUTHOR]