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

Background:In Behcet'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 unclassifiedBarnesiellaceaeandLachnospiragenera was associated with BD patients compared to HC. Subdivided by country, the Italian cohort displays a significant decrease of unclassifiedBarnesiellaceaeandLachnospiragenera, in the Dutch cohort this decrease is only a trend. Increased IgA-coating ofBifidobacteriumspp.,Doreaspp. andRuminococcus bromiispecies was found in stool from BD patients. Moreover, oral Dutch BD microbiome displayed increased abundance ofSpirochaetaceaeandDethiosulfovibrionaceaefamilies. Conclusions:BD patients show decreased fecal abundance ofBarnesiellaceaeandLachnospiraand increased oral abundance ofSpirochaetaceaeandDethiosulfovibrionaceae. In addition, increased fecal IgA coating ofBifidobacterium, Ruminococcus bromiiandDoreamay 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.