Salivary Microbiota Composition May Discriminate Between Patients With Eosinophilic Oesophagitis (EoE) and Non-EoE Subjects

Sonia Facchin; Matteo Calgaro; Mattia Pandolfo; Federico Caldart; Matteo Ghisa; Eliana Greco; Eleonora Sattin; Giorgio Valle; Evan S. Dellon; Nicola Vitulo; Edoardo Vincenzo Savarino

Disclosures

Aliment Pharmacol Ther. 2022;56(3):450-462. 

In This Article

Abstract and Introduction

Abstract

Background: Data on the role of the microbiome in adult patients with eosinophilic oesophagitis (EoE) are limited.

Aims: To prospectively collect and characterise the salivary, oesophageal and gastric microbiome in patients with EoE, further correlating the findings with disease activity.

Methods: Adult patients with symptoms of oesophageal dysfunction undergoing upper endoscopy were consecutively enrolled. Patients were classified as EoE patients, in case of more than 15 eosinophils per high-power field, or non-EoE controls, in case of lack of eosinophilic infiltration. Before and during endoscopy, saliva, oesophageal and gastric fundus biopsies were collected. Microbiota assessment was performed by 16 s rRNA analysis. A Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was implemented to identify biomarkers.

Results: Saliva samples were collected from 29 EoE patients and 20 non-EoE controls;, biopsies from 25 EoE and 5 non-EoE controls. In saliva samples, 23 Amplicon Sequence Variants (ASVs) were positively associated with EoE and 27 ASVs with controls, making it possible to discriminate between EoE and non-EoE patients with a classification error (CE) of 24%. In a validation cohort, the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of this model were 78.6%, 80%, 75%, 80% and 60%, respectively. Moreover, the analysis of oesophageal microbiota samples observed a clear microbial pattern able to discriminate between active and inactive EoE (CE = 8%).

Conclusion: Our preliminary data suggest that salivary metabarcoding analysis in combination with machine learning approaches could become a valid, cheap, non-invasive test to segregate between EoE and non-EoE patients.

Introduction

Eosinophilic oesophagitis (EoE) is an allergen/immune-mediated disease characterised by symptoms of oesophageal dysfunction and eosinophilic infiltration of the oesophageal mucosa in the absence of secondary causes of eosinophilia.[1] The prevalence (0.5–1 case per 1000) and the incidence (5–10 cases per 100,000 per year) markedly increased in the last decade and is now considered to be one of the most important causes of dysphagia in children and young adults. The diagnosis is based on suggestive clinical features (e.g. dysphagia and/or bolus impaction), the presence of eosinophilic inflammation (≥15 eosinophils per high-power field [eos/HPF] in at least one of multiple oesophageal biopsies) and exclusion of other causes of eosinophilia.[2,3] EoE affects more males than females (3:1), and the mean age at diagnosis is between 30 and 50 years in adults and 5 and 10 years among children.[4]

The pathogenesis is still uncertain. Among genetic factors, thymic stromal lymphopoietin (TSLP), Calpain 14 (CAPN14), chemokine C-C motif Ligand 26 (STAT6) appear to be involved in the development of EoE.[5,6] Moreover, environmental factors, including aero- and alimentary allergens, and early life conditions (Caesarean section, use of antibiotics, preterm birth) seem to have a predominant role in causing EoE and suggest that alterations in the microbiota may play a role in EoE pathogenesis.[7–9] In this context, the role of oesophageal microbiome has been evaluated in the evolution of this disease. In fact, a change in the composition or in the load of gastrointestinal microbiota has been involved in molecular pathogenic pathways and in promoting diseases.[10–12]

To date, little is known about the possible role of the gut microbiome in EoE, with most of the studies focusing on oesophageal and salivary microbiome.[13–17] These preliminary studies showed that active EoE is associated with an increase in Haemophilus, Neisseria and Corynebacterium in the oesophageal microbiome and, in contrast, inactive EoE patients and healthy controls have a predominance of Gram positive (especially Streptococcus) bacteria.[13–15,18] Comparing the salivary microbiome to the oesophageal one in paediatric EoE patients, a study demonstrated that both have an abundance of Streptococcus, Neisseria and Prevotella.[14] Moreover, there are no data on the composition of the gastric microbiome in EoE subjects, whereas in healthy subjects it seems to be composed by Actinobacteria (Rothia, Actinomyces and Micrococcus), Bacteroidetes (Prevotella), Firmicutes (Streptococcus and Bacillus) and Proteobacteria (H. pylori, Haemophilus, Actinobacillus and Neisseria).[19–22]

Given the limited knowledge about the characteristics of salivary, oesophageal and gastric microbiome in EoE and its correlation with the progression of the disease, we aimed to prospectively collect and characterise the salivary, gastric and oesophageal microbiome in active and inactive EoE patients, and to correlate these findings with disease activity.

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