Behçet's Disease Under Microbiotic Surveillance? A Combined Analysis of Two Cohorts of Behçet's Disease Patients.

Tim B Van Der Houwen,James Groot,Roos-Marijn Berbers,Clarissa Consolandi,Mario M D'Elios,Ad C Fluit,Guus H Van Muijlwijk,Marcel R De Zoete,Petrus M Van Hagen,Malbert Rogers,Jan A M Van Laar,C Marijn Hazelbag,Giacomo Emmi,Helen L Leavis,Marco Severgnini,Jasper H Kappen,Clelia Peano

doi:10.3389/fimmu.2020.01192

Abstract

Background: In Behçet's disease (BD), an auto-inflammatory vasculitis, an unbalanced gut microbiota can contribute to pro-inflammatory reactions. In separate studies, distinct pro- and anti-inflammatory bacteria associated with BD have been identified.Methods: To establish disease-associated determinants, we performed gut microbiome profiling in BD patients from the Netherlands (n = 19) and Italy (n = 13), matched healthy controls (HC) from the Netherlands (n = 17) and Italy (n = 15) and oral microbiome profiling in Dutch BD patients (n = 18) and HC (n = 15) by 16S rRNA gene sequencing. In addition, we used fecal IgA-SEQ analysis to identify specific IgA coated bacterial taxa in Dutch BD patients (n = 13) and HC (n = 8).Results: In BD stool samples alpha-diversity was conserved, whereas beta-diversity analysis showed no clustering based on disease, but a significant segregation by country of origin. Yet, a significant decrease of unclassified Barnesiellaceae and Lachnospira genera was associated with BD patients compared to HC. Subdivided by country, the Italian cohort displays a significant decrease of unclassified Barnesiellaceae and Lachnospira genera, in the Dutch cohort this decrease is only a trend. Increased IgA-coating of Bifidobacterium spp., Dorea spp. and Ruminococcus bromii species was found in stool from BD patients. Moreover, oral Dutch BD microbiome displayed increased abundance of Spirochaetaceae and Dethiosulfovibrionaceae families.Conclusions: BD patients show decreased fecal abundance of Barnesiellaceae and Lachnospira and increased oral abundance of Spirochaetaceae and Dethiosulfovibrionaceae. In addition, increased fecal IgA coating of Bifidobacterium, Ruminococcus bromii and Dorea may reflect retention of anti-inflammatory species and neutralization of pathosymbionts in BD, respectively. Additional studies are warranted to relate intestinal microbes with the significance of ethnicity, diet, medication and response with distinct pro- and inflammatory pathways in BD patients.

Highlights

Behçet’s disease (BD) is an auto-inflammatory vasculitis, characterized by mucosal ulcerations, skin lesions and uveitis [1]
Patients and Healthy controls (HC) were included in a Dutch and an Italian cohort
The Dutch cohort consisted of 19 patients [mean age: 50 years] and 17 age, gender- and ethnicity-matched HC; the Italian cohort of 14 patients [mean age: 45] and 15 age, gender- and ethnicity matched HC

Summary

Introduction

Behçet’s disease (BD) is an auto-inflammatory vasculitis, characterized by mucosal ulcerations, skin lesions and uveitis [1]. BD seems to be driven by an excessive T-cell reaction that might be triggered by an infectious antigen in a genetically susceptible host [3]. This is emphasized in the association with HLA-B51 and non-HLA genetic associations like IL10, IL23R, and ERAP1, which suggests a genetic susceptibility similar to spondyloarthritis [4]. In Behçet’s disease (BD), an auto-inflammatory vasculitis, an unbalanced gut microbiota can contribute to pro-inflammatory reactions. Distinct pro- and anti-inflammatory bacteria associated with BD have been identified

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