Introduction:Asthma is a multifactorial disease influenced by genetic and environmental factors, including diet. The gut microbiome contributes to airway inflammation via the gut-lung axis, partly through production of short chain fatty acids (SCFAs) from bacterial fermentation of dietary fiber. We hypothesized that dietary fiber supplementation could modulate the gut microbiome and increase SCFAs in children with asthma. Methods:This is a double-blind, placebo-controlled trial of children who were randomized to consume 12 g of soluble corn fiber (SCF) as a supplement to their usual daily diet (50% the recommended daily fiber intake) or placebo for 4-6 weeks (clinicaltrials.gov NCT03673618). Dietary surveys, asthma symptom questionnaires, fecal, blood and nasal samples were collected before and after the intervention period to quantify fiber intake, asthma control, nasal and gut microbiome, and serum short chain fatty acids (SCFAs). Results:Of the 20 children enrolled, 15 completed the intervention with an average adherence rate of 83%. SCFA concentrations and gut microbiome changes varied by individual and treatment group. No significant differences in gut or nasal alpha or beta diversity were observed between groups post-intervention. However, differential abundance analysis showed a trend toward increased Bifidobacterium in the SCF group compared to placebo (ANCOM-BC p = 0.0004, FDR q = 0.073). Discussion:Supplementation of 50% of recommended daily fiber intake had minimal impact on asthma symptoms, the microbiome, or SCFA levels. Future studies should consider higher fiber doses, different fiber types, or targeting individuals with low baseline fiber intake to account for observed variability in microbiome and SCFA responses. Clinical Trial Registration:https://clinicaltrials.gov/study/NCT03673618, identifier NCT03673618.

IgE-mediated food allergy and eosinophilic esophagitis (EoE) represent distinct yet interconnected manifestations of food-induced immune dysregulation. Rather than separate entities, emerging evidence supports a model that is on a continuum, in which clinical phenotypes are determined by antigen exposure patterns, dose, chronicity, and individual immune responses. This relationship has critical implications for food allergy immunotherapy, particularly oral immunotherapy. Among children with IgE-mediated food allergy, EoE prevalence is nearly 100-fold higher than the general population at 4.7%. During oral immunotherapy, gastrointestinal symptoms are common, with confirmed EoE developing in 1% to 10% of participants. Mechanistically, antigen avoidance favors IgE-mediated responses through T follicular helper cells, whereas sustained exposure promotes TH2-driven esophageal inflammation via pathogenic effector TH2 cells. Regulatory T-cell dysfunction appears central to this phenotypic switching. Clinical management requires risk stratification, systematic monitoring strategies, and individualized protocols that balance desensitization benefits against esophageal inflammation risks. Future directions include noninvasive diagnostic biomarkers, biologic therapies, and evidence-based prevention strategies. Understanding the food allergy-EoE continuum is essential for optimizing safety and efficacy of food allergen immunotherapy while minimizing complications.

BACKGROUND:Eosinophilic gastritis currently has no approved treatments and is postulated to be driven by type 2 inflammation. Dupilumab blocks type 2 cytokines IL-4 and IL-13 and has efficacy in multiple diseases characterised by type 2 inflammation, including eosinophilic oesophagitis. We aimed to assess the efficacy and safety of dupilumab in patients with eosinophilic gastritis. METHODS:DEGAS was a proof-of-concept, phase 2, multicentre, randomised controlled trial consisting of a 12-week, double-blind, placebo-controlled period, followed by a 24-week open-label extension period. Patients aged 12-70 years from 11 hospitals in the USA with histologically active eosinophilic gastritis (≥30 eosinophils per high-power field [HPF] in at least five HPFs in the gastric antrum and/or body) and moderate-to-severe symptoms occurring at least 2 days per week in the 2 weeks before screening were recruited. Patients with current or recent use of any biologic or current use of systemic steroids at a dose of more than 10 mg/day (prednisone) were excluded. Eligible patients were individually randomised (1:1) to parallel groups and received six injections over 12 weeks: subcutaneous dupilumab (600 mg once followed by 300 mg every 2 weeks) or subcutaneous placebo. Randomisation was performed using a central variable block (block sizes permuted between 2 and 4), with stratification by age (12-17 years or ≥18 years) and use (yes or no) of either systemic corticosteroids, swallowed corticosteroids for eosinophilic gastritis, or non-steroidal systemic immunosuppression therapy. Throughout the duration of the study, patients were expected to maintain their treatments or diets for eosinophilic gastritis. All patients who completed the double-blind period could enter the open-label extension at week 12, during which both groups received dupilumab until week 34. The primary endpoint of relative change from baseline in mean gastric eosinophil count from the five most eosinophil-dense HPFs in the gastric antrum and/or body was analysed at week 12 using linear regression. Secondary endpoints included absolute changes from baseline in Eosinophilic Gastritis Histologic Scoring System (EoS-HSS) total score, mean gastric eosinophil count from the five most eosinophil-dense HPFs, and Eosinophilic Gastritis Endoscopic Reference System (EoG-REFS) total score. All randomly assigned patients who received at least one dose of study drug were included in the safety analysis and efficacy analyses were done in all randomly assigned patients who received at least one dose of study drug and had outcome data available at week 12 (complete case). This study is registered with ClinicalTrials.gov (NCT03678545) and is now complete. FINDINGS:Between May 14, 2021, and Nov 10, 2023, we randomly assigned 41 patients, of whom 21 (51%) received dupilumab and 20 (49%) received placebo during the double-blind period and were included in the safety analysis. Patients were aged 12-59 years (mean 30·5 years [SD 13·2]; seven [17%] aged <18 years), 37 (90%) were White, one (2%) was Asian, one (2%) was Black or African American, two (5%) were of multiple races, 25 (61%) were female, and 16 (39%) were male. One patient from the placebo group withdrew before week 12; the remaining 21 patients treated with dupilumab and 19 patients treated with placebo had available data and were assessed for the primary endpoint. At week 12, the relative reduction in the primary endpoint was greater with dupilumab (estimated mean change -50% [95% CI -66 to -34]) than with placebo (-4% [-20 to 13]; difference -47 percentage points [-70 to -24]; p<0·0001). Significant differences between groups were noted for the secondary endpoints of absolute change from baseline in EoS-HSS total score (difference -0·10 [95% CI -0·18 to -0·03]; p=0·0055), absolute change from baseline in mean gastric eosinophil count (-38·8 [-75·6 to -17·8]; p=0·0008), and absolute change from baseline in EoG-REFS total score (-3·42 [-6·18 to -0·65]; p=0·016). At week 12, the incidence of treatment-emergent adverse events was similar between dupilumab (17 [81%]) and placebo (17 [85%]). The most common adverse event was blood eosinophilia, with similar incidence in the dupilumab (six [29%]) and placebo (six [30%]) groups. No serious adverse events or treatment-related deaths were reported. INTERPRETATION:The improvement of histological outcomes of eosinophilic gastritis with dupilumab in this proof-of-concept study shows type 2 inflammatory involvement in the disease and the potential value of dupilumab for the treatment of eosinophilic gastritis. FUNDING:National Institutes of Health, USA; Regeneron Pharmaceuticals Inc; and Sanofi.

Food allergies are a significant public health concern in the United States. Fatality from food-induced anaphylaxis is associated with delayed administration of epinephrine. Utah children were at increased risk for school-related anaphylaxis due to a lack of school nurses, adequately trained staff, and a standardized approach to food allergy emergency management. In collaboration with the Utah School Nurses Association, the Utah Food Allergy Network, and the Utah Department of Health & Human Services, among other contributors, we aimed to accomplish the following goals: (1) develop and implement a web-based curriculum to train school staff to recognize and respond to anaphylaxis in school settings; (2) educate school officials on existing legal protections for layperson first responders; and (3) facilitate acquisition of unassigned epinephrine for use in schools through existing charitable pharmaceutical programs. From 2012 to 2023, our training program was completed 5759 times by individuals representing 421 Utah schools. The course was most frequently completed by teachers (n = 3006, 52.2%), office staff (n = 1480, 25.7%), and principals (n = 276, 4.8%). Since 2015, we have maintained an average year-to-year retention rate of greater than 68%. We observed a 245% increase in the number of schools with unassigned epinephrine. Due to this intervention, many Utah schools now prepare employees to administer epinephrine in the case of anaphylactic emergencies. Although school nurses play a significant role, their coverage is inadequate to meet the needs of all students at risk for anaphylaxis. Training volunteers to recognize and respond to anaphylaxis in school settings is needed to reduce delays in treatment and improve outcomes.

BACKGROUND:Less invasive diagnostics that decrease dependence on sedated endoscopy are needed for eosinophilic esophagitis (EoE). OBJECTIVE:To review the literature describing alternatives to conventional upper endoscopy in EoE. DATA SOURCES:A literature search was conducted using MEDLINE for articles published through March 2026. STUDY SELECTIONS:Articles were considered for inclusion if they evaluated clinically available minimally invasive diagnostic tools or noninvasive biomarkers under investigation for EoE. Both adult and pediatric studies were considered. Case reports/series were excluded. METHODS:Studies were grouped into categories, including minimally invasive sampling devices and noninvasive biomarkers. Noninvasive biomarkers were further subdivided into biomarkers for screening, surveillance, and prognostication. Data were qualitatively synthesized given the heterogeneity in study design and outcomes. RESULTS:Unsedated transnasal endoscopy (TNE) and the esophageal string test (EST) are clinically available, minimally invasive surrogates for conventional sedated endoscopy. Completion rates are high for TNE (>95%) and the EST (>86%). Both are well tolerated and reduce overall visit time and cost. TNE and EST are best suited for disease monitoring in adolescents and adults after EoE is diagnosed. Eosinophil counts, eosinophil-derived proteins, and eosinophil activation markers are the most widely investigated noninvasive blood biomarkers. RNA and microRNA biomarkers and specific cell types (eg, pathogenic effector TH2 cells) may have superior diagnostic performance. Most biomarker studies are limited by the omission of allergic controls. CONCLUSION:Minimally invasive diagnostics can be implemented to monitor EoE disease activity. Additional studies with allergic controls are needed to validate noninvasive EoE biomarkers for screening, surveillance, and predicting disease/treatment outcomes.

OBJECTIVES:Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease with rising incidence globally. Described predominantly in White populations, the clinical features of EoE in Hispanic children are poorly characterized. This study evaluated the clinical, endoscopic, histologic, and treatment characteristics of Hispanic versus Non-Hispanic pediatric patients with EoE. METHODS:We conducted a retrospective comparative cohort study of pediatric patients newly diagnosed with EoE. Hispanic patients were compared 1:1 with non-Hispanic. Clinical, atopic, endoscopic, histologic, and treatment data were abstracted from medical records. Multivariate logistic regression identified features associated with Hispanic ethnicity. RESULTS:One hundred and eighty-six patients (93 Hispanic, 93 non-Hispanic) were included. Hispanic patients had longer symptom duration before diagnosis, were more likely to present with weight loss (odds ratio [OR] 10.16, 95% confidence interval [CI] 3.00-34.41) and asthma (OR 3.7, 95% CI 1.28-10.66), and less likely to have immunoglobulin E-mediated food allergy (OR 0.07, 95% CI 0.02-0.23). Endoscopically, they were more likely to have a normal-appearing esophagus (OR 21.07, 95% CI 3.47-127.83) with fewer furrows; however, when abnormal endoscopic findings were present, exudates were more common (OR 3.3, 95% CI 1.06-10.28). Histologic activity was comparable across groups. Treatment responses were similar overall, though remission with proton pump inhibitors was more common in Hispanic patients. CONCLUSIONS:Hispanic pediatric patients with EoE exhibit distinct clinical features, which may reflect differences in clinical presentation and healthcare-related factors that were not directly measured. These observations underscore the need for heightened clinical awareness and tailored strategies to reduce disparities in diagnosis and access to care among Hispanic patients.

BACKGROUND:Eosinophilic esophagitis is associated with epithelial barrier dysfunction. Epidemiologic studies suggest environmental factors promote disease pathogenesis. The common household detergent sodium dodecyl sulfate (SDS) induces epithelial barrier dysfunction and eosinophilic inflammation in mice. We hypothesized that acute SDS exposure would compromise the esophageal mucosal barrier in humans. METHODS:Healthy adults brushed with 2 g of an SDS-containing toothpaste. Esophageal impedance was measured continuously pre-/post-toothbrushing to assess the effect of toothpaste on epithelial barrier function. SDS was measured in saliva using a methylene blue anionic substances assay. Participants completed 1-h esophageal string tests (ESTs) pre-/post-toothbrushing and protein isolates from EST eluates from the proximal and distal esophagus were analyzed by tandem mass tag mass spectrometry. RESULTS:Ten of twelve subjects completed the clinical study. SDS in the initial expectorate measured immediately after toothbrushing varied markedly (median: 321.40 μg/mL; range: 169.90-1243.00 μg/mL) and was detectable in saliva in 80% of subjects (median: 9.55 μg/mL; range: 0-123.40 μg/mL) at 60 min post toothbrushing. Esophageal mucosal impedance decreased within 30 min of toothbrushing (p < 0.01). Toothbrushing increased salivary viscosity and proteins associated with mucosal defense in EST eluates. The tight junction pathway was downregulated while the salivary secretion and complement and coagulation cascades pathways were upregulated in the proximal esophagus. CONCLUSION:In healthy individuals, SDS remained detectable in saliva for a prolonged period after toothbrushing at concentrations previously shown to disrupt esophageal epithelial barrier function in vitro. Toothbrushing with an SDS-containing toothpaste was associated with reduced esophageal mucosal impedance, altered salivary properties, and activated mucosal immune responses.

In January 2025, the American College of Gastroenterology published updated guidelines on the diagnosis and management of eosinophilic esophagitis (EoE). These new guidelines incorporated updated information on the pathophysiology, risk factors, natural history, and treatment of EoE. These guidelines were primarily intended for practicing gastroenterologists; therefore, we summarize their key recommendations for the allergy and immunology community. In addition, as the prevalence and health care burden of EoE continues to increase, the population affected primarily comprises allergic individuals, and less invasive monitoring techniques are on the horizon, we discuss the key means by which allergists can contribute to the diagnosis and management of EoE. In particular, allergists can participate in screening for subtle EoE symptoms among their allergy patients, assist in optimizing the management of other allergic comorbidities, provide education about elimination diets, and facilitate the monitoring of disease over time. Allergists are uniquely poised to treat the entire allergic individual, rather than just the allergic esophagus, and should be prepared to co-manage these patients along with gastroenterologists.

BACKGROUND:Eosinophils have specific immune phenotypes in type 2 and type 1 environments. The regulatory transcription factors (TFs) that control eosinophil activation in type 2 or type 1 immune phenotypes E2 (eosinophils treated with IL-4, GM-CSF, IL-33, and IL-5) or E1 (eosinophils treated with IFN-γ, TNF-α, and IL-5), respectively, are unknown. OBJECTIVE:We sought to compare mouse and human eosinophil immune phenotypes following exposure to type 2 or type 1 polarizing cytokines and identify TFs that may regulate these responses. METHODS:Peripheral blood eosinophils were isolated from wild-type mice and from healthy human donors. Cells were cultured with type 2 (IL-4, GM-CSF, and IL-33) or type 1 (IFN-γ and TNF-α) cytokines. Cells underwent characterization of morphology, gene or protein expression, and bulk RNA sequencing. Bone marrow-derived wild-type and interferon regulatory factor (IRF)-deficient mouse eosinophils were generated and analyzed. RESULTS:Mouse and human eosinophils both demonstrated type 2 or type 1 cytokine/chemokine production as per E2 or E1 condition. Gene set enrichment revealed that similar pathways were upregulated in mouse and human E2 or E1 eosinophils, respectively. Upstream TF regulatory networks were identified as similar between species as per E2 or E1 condition. In particular, IRF1 expression increased significantly in E1 conditions for mouse and human eosinophils. IRF1-deficient mouse eosinophils had significant increases in type 2 cytokine and chemokine production concurrent with reduced Nos2, Stat1, IL-12b, and PDL1 when in E1 conditions. CONCLUSIONS:Mouse and human eosinophils have significant similarities in their transcriptomes for their responses to type 2 and type 1 cytokines. IRF1 is increased in mouse and human eosinophils in type 1 environments and regulates immune responses of mouse eosinophils stimulated with type 1 cytokines.

BACKGROUND AND AIMS:Eosinophilic esophagitis (EoE) is a chronic, inflammatory, and antigen-driven disease of the esophagus. Total transcriptome data revealed alterations in the endocannabinoid system, in particular, down-regulation of monoacylglycerol lipase (MGL) in biopsies of patients with active EoE. We investigated the consequence of MGL down-regulation in mucosal biopsies of patients, and its implications for EoE development, such as recruitment of eosinophils. METHODS:Levels of MGL substrate 2-arachidonoylglycerol, MGL enzyme activity, and MGL colocalization with epithelial cells were determined in mucosal esophageal biopsies of patients with EoE. Supernatant of human primary esophageal epithelial cells was used to determine eosinophil migration and activation. An inducible mouse model of EoE was used to test MGL inhibition and cannabinoid (CB) receptor antagonism in vivo. RESULTS:MGL expression in esophageal epithelial cells from patients with active EoE is decreased, whereas 2-arachidonoylglycerol is increased compared with control subjects. Inhibition of MGL in epithelial cells leads to a proinflammatory phenotype capable of attracting eosinophils via CB2. Similarly, the EoE mouse model indicates that absence of MGL results in higher eosinophil infiltration. Targeting CB2 reduced the number of infiltrating eosinophils in the esophagi of mice. CONCLUSIONS:This study is the first of its kind to investigate the involvement of altered expression of endocannabinoid system components in EoE, and partly explains recent findings of more inflammatory features post EoE-treatment in cannabis users. Our findings could pave the way for research into alternative treatment options for EoE and call for caution regarding the use of cannabinoids in EoE.