Children with eosinophilic esophagitis non-responsive to combination therapy have distinct esophageal transcriptomic and microbiome profile.

BACKGROUND: A combination of proton-pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non-responders (EoE-PPI-TSnr; n = 7) and responders (EoE-PPI-TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics. METHODS: Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. RESULTS: In all, 3164 upregulated and 3154 downregulated genes distinguished EoE-PPI-TSnr from EoE-PPI-TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE-PPI-TSnr. There was a 56% overlap in dysregulated genes between EoE-PPI-TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic-erythroid progenitors, and T helper type 1 cells were significantly higher in EoE-PPI-TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE-PPI-TSnr and correlated with the key pathways. CONCLUSION: Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.

Causality of Helicobacter pylori infection on eosinophilic esophagitis and potential pathogenesis: a Mendelian randomization study.

Background: Observational studies have indicated a possible connection between Helicobacter pylori (H. pylori) infection and eosinophilic esophagitis (EoE), but their causal relationship has yet to be established. To investigate the causal associations between H. pylori infection and EoE, we performed a Mendelian randomization (MR) analysis. Methods: Firstly, we conducted both univariable and multivariable Mendelian randomization (MR) analyses. Furthermore, a two-step MR was carried out to ascertain the potential underlying pathways of these associations, particularly the involvement of inflammatory cytokines. We employed the inverse-variance weighted (IVW) method as the main analysis in our MR study. To enhance the credibility of the results, we also conducted several sensitivity analyses. Results: Our study demonstrated a noteworthy correlation between genetically predicted anti-H. pylori IgG antibody levels and a reduced risk of EoE (OR=0.325, 95% CI=0.165-0.643, P value=0.004, adj p value=0.009). No significant causal associations were detected between other H. pylori antibodies and EoE in our study. When it comes to multivariable MR analysis controlling for education attainment, household income, and deprivation individually, the independent causal impact of anti-H. pylori IgG on EoE persisted. Surprisingly, the two-step MR analysis indicated that inflammatory factors (IL-4, IL-5, IL-13, IL-17, and IFN-γ) did not appear to mediate the protective effect of H. pylori infection against EoE. Conclusion: Findings suggested that among the range of H. pylori-related antibodies, anti-H. pylori IgG antibody is the sole causal factor associated with protection against EoE. Certain inflammatory factors may not be involved in mediating this association. These findings make a significant contribution to advancing our understanding of the pathogenesis of EoE and its evolving etiology.

Host-Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation.

BACKGROUND & AIMS: Microbiota composition and mechanisms of host-microbiota interactions in the esophagus are unclear. We aimed to uncover fundamental information about the esophageal microbiome and its potential significance to eosinophilic esophagitis (EoE). METHODS: Microbiota composition, transplantation potential, and antibiotic responsiveness in the esophagus were established via 16S ribosomal RNA sequencing. Functional outcomes of microbiota colonization were assessed by RNA sequencing analysis of mouse esophageal epithelium and compared with the human EoE transcriptome. The impact of dysbiosis was assessed using a preclinical model of EoE. RESULTS: We found that the murine esophagus is colonized with diverse microbial communities within the first month of life. The esophageal microbiota is distinct, dominated by Lactobacillales, and demonstrates spatial heterogeneity as the proximal and distal esophagus are enriched in Bifidobacteriales and Lactobacillales, respectively. Fecal matter transplantation restores the esophageal microbiota, demonstrating that the local environment drives diversity. Microbiota colonization modifies esophageal tissue morphology and gene expression that is enriched in pathways associated with epithelial barrier function and overlapping with genes involved in EoE, including POSTN, KLK5, and HIF1A. Finally, neonatal antibiotic treatment reduces the abundance of Lactobacillales and exaggerates type 2 inflammation in the esophagus. Clinical data substantiated loss of esophageal Lactobacillales in EoE compared with controls. CONCLUSIONS: The esophagus has a unique microbiome with notable differences between its proximal and distal regions. Fecal matter transplantation restores the esophageal microbiome. Antibiotic-induced dysbiosis exacerbates disease in a murine model of EoE. Collectively, these data establish the composition, transplantation potential, antibiotic responsiveness, and host-microbiota interaction in the esophagus and have implications for gastrointestinal health and disease.

Esophageal microbiome in active eosinophilic esophagitis and changes induced by different therapies.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory esophageal disease triggered by food antigens. Cumulative evidence supports the implication of microbiota and the innate immune system in the pathogenesis of EoE. Changes in the esophageal microbiome were investigated by applying 16S rRNA gene sequencing on esophageal biopsies of adult patients with active EoE at baseline (n = 30), and after achieving remission with either proton pump inhibitors (PPI, n = 10), swallowed topical corticosteroids (STC, n = 10) or food-elimination diets (FED, n = 10). Ten non-EoE biopsies were also characterized as controls. Compared to controls, no differences in alpha (intra-sample) diversity were found in EoE microbiota overall. However, it decreased significantly among patients who underwent FED. As for beta (inter-sample) diversity, non-EoE controls separated from EoE baseline samples. Post-treatment samples from patients treated with PPI and FED had a more similar microbiota composition, while those receiving STC were closer to controls. Differential testing of microbial relative abundance displayed significant changes for Filifactor, Parvimonas and Porphyromonas genera. Analysis of predicted functions indicated alterations in metabolic pathways and abundance of sulphur-cytochrome oxidoreductases. Our findings demonstrate changes in microbiota associated with EoE, as well as a treatment effect on the microbiome.

Epidemiology and risk factors for eosinophilic esophagitis: lessons for clinicians.

INTRODUCTION: The rapid expansion in the epidemiology of eosinophilic esophagitis (EoE) is being documented, along with cumulative research assessing environmental exposures associated with EoE and susceptibility due to genetic variants. AREAS COVERED: Incidence rates for EoE of 5-10 new cases per 100,000 inhabitants annually have shown an increase in recent reports of up to 20 in some countries; the highest prevalence being reported for Europe and North America, where EoE now affects more than 1 out of 1,000 people. EoE has been shown to be associated with several disorders, Th2-mediated atopies being the most common. Patients with EoE exhibit increased frequency of asthma, allergic rhinitis and eczema, and EoE has been considered as a late component of the atopic march. Risk variants in TSLP, CAPN14 and LRCC32 genes, among others, have all been related to EoE, and interact with prenatal and early life exposure potentially modifying abundance and composition of gut microbiome. Dysregulated interactions between bacteria and mucosal immunity emerge as leading causes of EoE. EXPERT OPINION: The expanding epidemiology of EoE, the resources needed and subsequent increasing healthcare costs require additional effort to optimize cost-effective management and unveil mechanisms that enhance the development of future preventive strategies.

Reconsidering the "protective" hypothesis of Helicobacter pylori infection in eosinophilic esophagitis.

Since its discovery, Helicobacter pylori (H. pylori) has attracted attention in the biomedical world with its numerous pathophysiologic implications, both gastrointestinal and systemic. Beyond its well-established carcinogenic properties, emerging evidence also supports "harmful" proinflammatory and neurodegenerative roles of H. pylori. On the other hand, H. pylori infection has been proposed to be "protective" against several diseases, such as asthma and gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) is a relatively new, allergen/immune-mediated disease, which has also been linked to these considerations. Main arguments are a postulated shift of immune responses by H. pylori from T helper 2 (TH 2) to TH 1 polarization, as well as a potential decline of the H. pylori burden with the dramatic parallel rise of ΕοΕ: a series of observational studies reported an inverse association. In this review, we counter these arguments by providing further epidemiological data, which point out that this generalization might be rather incomplete. We also discuss the limitations of the existing studies evaluating a possible association. Furthermore, we provide current evidence on common pathogenetic components, which share both entities. In summary, the claim that H. pylori is protective against EoE is rather incomplete, and further mechanistic studies are necessary to elucidate a possible association.

Microbiota in non-IgE-mediated food allergy.

PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy. RECENT FINDINGS: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota. SUMMARY: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

Relationship of the Esophageal Microbiome and Tissue Gene Expression and Links to the Oral Microbiome: A Randomized Clinical Trial.

INTRODUCTION: Although the microbiome is altered in various esophageal diseases, there is no direct evidence for a link between the oral or esophageal microbiome and underlying esophageal tissue. Here, we aimed to address these gaps through use of an antimicrobial mouth rinse to modify the esophageal microbiome and tissue gene expression. METHODS: In this randomized controlled trial, patients scheduled to undergo endoscopy for clinical indications used chlorhexidine mouth rinse or no treatment for 2 weeks before endoscopy. Oral swabs and saliva were collected at baseline and at follow-up, and the esophagus was sampled on the day of endoscopy. The microbiome was analyzed by 16S rRNA gene sequencing, and esophageal tissue gene expression was ascertained by RNA-Seq. RESULTS: Twenty subjects were enrolled and included in the analyses. Within individuals, the oral and esophageal microbiome composition was significantly correlated. Chlorhexidine treatment associated with significant alterations to the relative abundance of several esophageal bacterial taxa, and to expression of genes in the esophagus including reductions in periostin, claudin-18, chemokines CXCL1 and CXCL13, and several members of the tumor necrosis factor receptor superfamily. A taxon in genus Haemophilus in the esophagus also associated with significant changes in tissue gene expression. DISCUSSION: The oral and esophageal microbiomes are closely related within individuals, and esophageal microbiome alterations correlate with tissue gene expression changes. The esophageal microbiome may act as an important cofactor that influences pathogenesis and outcomes of diseases such as eosinophilic esophagitis, gastroesophageal reflux, and Barrett's esophagus.

A decreased abundance of clostridia characterizes the gut microbiota in eosinophilic esophagitis.

Abnormalities in the gut microbiome are associated with suppressed Th2 response (Belizario et al., 2018 Mediators Inflamm. 2018:2037838) and predisposition to atopic disease such as asthma and eczema. We investigated if this applies to eosinophilic esophagitis (EoE). Stool bacterial DNA was extracted and followed by 16S rRNA amplification from 12 patients with eosinophilic esophagitis and 12 controls. Alpha- and beta-diversity were analyzed. Only two patients had asthma or atopy and one patient was on budesonide. No patients were on PPIs. Patients with EoE had lower gut microbiota alpha diversity (species richness, P = 0.09; Shannon index, P = 0.01). The microbial composition was distinct as evidenced by significantly different beta diversity (P = 0.03) when compared to healthy controls. There were also significant differences in relative abundance at multiple taxonomic levels when comparing the two communities; at the phylum level, we observed a marked decrease in Firmicutes and increase in Bacteroidetes and at the order and family level there were significant decreases in Clostridia and Clostridiales in patients with EoE (q ≤ 0.1). We conclude that there are significant differences in microbial community structure, microbial richness, and evenness and a significant decrease in taxa within the Clostridia in patients with EoE. Our data suggest that Clostridia based interventions could be tested as adjuncts to current therapeutic strategies in EoE.

The Salivary Microbiome Is Altered in Children With Eosinophilic Esophagitis and Correlates With Disease Activity.

OBJECTIVES: Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease affecting the esophagus. Although microbial communities may affect the host immune responses, little is known about the role of the microbiome in EoE. We compared the composition of the salivary microbiome in children with EoE with that of non-EoE controls to test the hypotheses that the salivary microbiome is altered in children with EoE and is associated with disease activity. METHODS: Saliva samples were collected from 26 children with EoE and 19 non-EoE controls comparable for age and ethnicity. The salivary microbiome was profiled using 16S rRNA gene sequencing. Disease activity was assessed using the Eosinophilic Esophagitis Endoscopic Reference Score and the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). RESULTS: A trend toward lower microbial richness and alpha diversity was noted in children with EoE. Although the overall salivary microbiome composition was similar between children with and without EoE, specific taxa such as Streptococcus (q value = 0.06) tended to be abundant in children with active EoE compared with non-EoE controls. Haemophilus was significantly abundant in children with active EoE compared with inactive EoE (q value = 0.0008) and increased with the increasing EoEHSS and Eosinophilic Esophagitis Histology Scoring System (q value = 5e-10). In addition, 4 broad salivary microbial communities correlated with the EoEHSS. DISCUSSION: The composition of the salivary microbiome community structure can be altered in children with EoE. A relative abundance of Haemophilus positively correlates with the disease activity. These findings indicate that perturbations in the salivary microbiome may have a role in EoE pathobiology and could serve as a noninvasive marker of disease activity.

Allergic Comorbidity in Eosinophilic Esophagitis: Mechanistic Relevance and Clinical Implications.

Allergic eosinophilic esophagitis (EoE) is a chronic, allergen-mediated inflammatory disease of the esophagus, and the most common cause of prolonged dysphagia in children and young adults in the developed world. While initially undistinguished from gastroesophageal reflux disease-associated esophageal eosinophilia, EoE is now recognized as a clinically distinct entity that shares fundamental inflammatory features of other allergic conditions and is similarly increasing in incidence and prevalence. The clinical and epidemiologic associations between EoE and other allergic manifestations are well established. In addition to exaggerated rates of atopic dermatitis, IgE-mediated food allergy, asthma, and allergic rhinitis in EoE patients, each of these allergic manifestations imparts individual and cumulative risk for subsequent EoE diagnosis. As such, EoE may be a member of the "allergic march"-the natural history of allergic manifestations during childhood. Several determinants likely contribute to the relationship between these conditions, including shared genetic, environmental, and immunologic factors. Herein, we present a comprehensive review of allergic comorbidity in EoE. We discuss areas of the genome associated with both EoE and other allergic diseases, including the well-studied variants encoding thymic stromal lymphopoietin and calpain 14, among other "atopic" regions. We summarize ways that environmental factors (such as microbiome-altering pressures and aeroallergen exposure) may predispose to multiple allergic conditions including EoE. Finally, we touch on some fundamental features of type 2 inflammation, and the resulting implications for the development of multiple allergic manifestations. We conclude with an analysis of the "type 2" biologics, and how mechanistic similarities between EoE and the other allergic manifestations have important implications for screening and treatment of the allergic patient.

The Esophageal Microbiome in Health and Disease.

PURPOSE OF REVIEW: Investigation of the esophageal microbiome is a relatively new field. This review will outline data characterizing the esophageal microbiome in both health and disease states, including gastroesophageal reflux disease (GERD), Barrett's esophagus, esophageal cancer, eosinophilic esophagitis, and motility disorders. RECENT FINDINGS: While the esophagus was previously considered devoid of a significant bacterial population, development of culture-independent techniques, specifically 16S rRNA gene sequencing, as well as novel, minimally invasive microbial sampling modalities, has facilitated characterization of the esophageal microbiome in both health and several disease states. Although limited, there is evidence that the esophagus contains a diverse microbial population, with Gram-positive bacteria, specifically Streptococcus, dominating in health, while Gram-negative bacteria prevail in reflux disorders including GERD and Barrett's esophagus. The microbiome is altered with other esophageal disorders as well, including eosinophilic esophagitis and esophageal motility disorders, though these changes have been less well characterized. Characterization of the gut microbiome has advanced significantly; however, further investigation is essential. Understanding changes in the esophageal microbiome could affect our understanding of the natural history of diseases of the esophagus and present potential therapeutic approaches.

Unique causes of esophageal inflammation: a histopathologic perspective.

Gastroenterologists frequently perform endoscopic esophageal mucosal biopsies for pathologic diagnosis in patients experiencing symptoms of esophagitis. The more common causes of esophagitis diagnosed on esophageal mucosal biopsy include reflux esophagitis, eosinophilic esophagitis, and infectious esophagitis caused by Candida albicans, herpes simplex virus, and/or cytomegalovirus. However, there are several causes of esophagitis seen less frequently by pathologists that are very important to recognize. We discuss unique types of esophageal inflammation, including acute bacterial esophagitis, esophageal manifestations of dermatologic diseases, medication-induced esophageal injury, and sloughing esophagitis; and we review their clinical and histopathologic features.

The cultivable bacterial flora of the esophagus in subjects with esophagitis.

BACKGROUND: The healthy human esophagus is colonized by bacteria similar to that of the oral mucosa. However, little is known about the microbiome of the esophagus in esophagitis or the possible role of bacteria in the inflammatory response. AIM: To survey bacterial diversity and compare the microbiome of the esophagus in subjects with gastro-esophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). MATERIAL AND METHODS: Seventeen subjects diagnosed with GERD and 10 with EoE underwent endoscopic examination with brush sampling and biopsies from the oral cavity, upper and lower esophagus. The samples were cultivated on agar plates, and bacterial growth was identified to the genus or species level and semi-quantified. RESULTS: Significantly higher numbers of bacterial groups or species were found in specimens from the lower esophagus in subjects with EoE compared to subjects with GERD (median 4 (range 1-7) vs. 2 (range 0-6), p < .0014). Sixteen vs. 14 different bacterial groups or species were found in subjects with GERD and EoE, respectively, mostly in sparse or very sparse amounts. Alfa-streptococci (viridans streptococci) were the most common bacteria in both groups. Streptococci were present in all of the EoE-subjects but only in approximately 75% in lower esophagus of the GERD-subjects, regardless of the sampling method. CONCLUSION: Subjects with GERD had significantly less bacterial diversity in both oral and esophageal samples than EoE-subjects. Whether this discrepancy might be explained by an effect on the protective mucosal biofilm by the acidic content of the reflux in subjects with GERD remains unclear.

Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis.

OBJECTIVES: Esophageal microbiota and regulation of adaptive immunity are increasingly being investigated in eosinophilic esophagitis (EoE). Toll-like receptors (TLRs) play a central role in the initiation and maintenance of innate immune activity. Our objective was to characterize the esophageal and duodenal innate immune response in EoE and its modulation by dietary therapy. METHODS: Esophageal and duodenal biopsy samples were collected from 10 adults with untreated EoE, before and after effective treatment with a six-food elimination diet (SFED), and 10 controls with normal esophagus. In all cases, bacterial load (by mRNA expression of 16S), TLRs, mucins, transcription factors, interleukins, components of the NKG2D system, and innate immunity effectors were assessed by qPCR. Protein expression of TLRs were also determined by immunofluorescence. RESULTS: Bacterial load and TLR1, TLR2, TLR4, and TLR9 were overexpressed on biopsies with active EoE compared with controls. Muc1 and Muc5B genes were downregulated while Muc4 was overexpressed. Upregulation of MyD88 and NFκB was found together with IL-1ß, IL-6, IL-8, and IL-10 mediators and PER-1, iNOS, and GRZA effectors. NG-K2D components (KLRK1, IL-15, MICB) were also upregulated. In all cases, changes in active EoE were normalized following SFED and mucosal healing. Duodenal samples also showed increased expressions of TLR-1, TLR-2, and TLR-4, but not 16S or any other mediators nor effectors of inflammation. CONCLUSIONS: Esophageal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease.

Elevated IL-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous IL-33 promotes eosinophilic esophagitis development in mice.

We tested whether the T helper (Th) type 2 (Th2) cell agonist and allergenic ligand IL-33 was associated with eosinophilic esophagitis (EoE) development in a pediatric cohort and whether IL-33 protein could induce disease symptoms in mice. Biopsies from EoE patients or controls were used to measure IL-33 mRNA and protein expression. Increased expression of IL-33 mRNA was found in the esophageal mucosa in EoE. IL-33 protein was detected in cells negative for CD45, mast cells, and epithelial cell markers near blood vessels. Circulating levels of IL-33 were not increased. The time course for IL-33 gene expression was quantified in an established Aspergillus fumigatus allergen mouse model of EoE. Because IL-33 induction was transient in this model and chronicity of IL-33 expression has been demonstrated in humans, naive mice were treated with recombinant IL-33 for 1 wk and esophageal pathology was evaluated. IL-33 application produced changes consistent with phenotypically early EoE, including transmural eosinophilia, mucosal hyperproliferation, and upregulation of eosinophilic genes and chemokines. Th2 cytokines, including IL-13, along with innate lymphoid cell group 2, Th1/17, and M2 macrophage marker genes, were increased after IL-33 application. IL-33-induced eosinophilia was ablated in IL-13 null mice. In addition, IL-33 induced a profound inhibition of the regulatory T cell gene signature. We conclude that IL-33 gene expression is associated with pediatric EoE development and that application of recombinant protein in mice phenocopies the early clinical phase of the human disease in an IL-13-dependent manner. IL-33 inhibition of esophageal regulatory T cell function may induce loss of antigenic tolerance, thereby providing a mechanistic rationale for EoE development.

Esophageal microbiome in eosinophilic esophagitis.

OBJECTIVE: The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. DESIGN: In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. RESULTS: Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. CONCLUSIONS: Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.

Inverse association of esophageal eosinophilia with Helicobacter pylori based on analysis of a US pathology database.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is of increasing prevalence and believed to result from allergic processes. Helicobacter pylori has been inversely associated with allergic diseases, but there is no known relationship between H pylori, EoE, and esophageal eosinophilia. We investigated the association between esophageal eosinophilia and H pylori infection. METHODS: We performed a cross-sectional study of data, collected from a US pathology database, on 165,017 patients in the United States who underwent esophageal and gastric biopsies from 2008 through 2010. Patients with and without H pylori on gastric biopsy were compared, and odds of esophageal eosinophilia were determined. RESULTS: From the data analyzed, 56,301 (34.1%) had normal esophageal biopsy specimens, 5767 (3.5%) had esophageal eosinophilia, and 11,170 (6.8%) had H pylori infection. Esophageal eosinophilia was inversely associated with H pylori (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.69-0.87). Compared with patients with normal esophageal biopsy specimens, odds of H pylori were reduced among patients with ≥ 15 eosinophils per high-power field (eos/hpf) (OR, 0.79; 95% CI, 0.70-0.88), ≥ 45 eos/hpf (OR, 0.75; 95% CI, 0.61-0.93), ≥ 75 eos/hpf (OR, 0.72; 95% CI, 0.50-1.03), and ≥ 90 eos/hpf (OR, 0.52; 95% CI, 0.31-0.87) (P for trend <.001). A similar dose-response trend was observed for increasing clinical suspicion for EoE and decreasing prevalence of H pylori. Additionally, severity of histologic effects of H pylori was inversely associated with esophageal eosinophilia. All trends held in multivariate analysis. CONCLUSIONS: In a large cross-sectional analysis, H pylori infection was inversely associated with esophageal eosinophilia. This relationship could have implications for the pathogenesis and epidemiology of EoE.