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

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, van der Houwen et al. Microbiota in Behçet's Disease 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.

Behçet’s Disease—Do Microbiomes and Genetics Collaborate in Pathogenesis?

“…and reduced presence of IgA-coated Erysipelotrichaceae spp. in the Dutch BD cohort compared to healthy controls, although this was not analyzed in the Italian cohort (14). These data support the requirement for more, larger studies to determine the geographical and environmental changes compared to disease-induced changes in the BD gut microbiome.…”

Interrelationship of Stress, Environment, and Herpes Simplex Virus Type-1 on Behçet’s Disease: Using a Mouse Model

“…Many researchers expect that microbiota can explain differences in the incidence of BD under various environmental conditions of different regions. Dysbiosis of the gut microbiome may trigger or exacerbate the inflammatory process in BD, and a reduced intestinal microbial diversity was observed in patients with BD ( 27 ). In an animal study, fecal microbiota transplantation using feces from BD patients has been shown to significantly exacerbate uveitis ( 16 ).…”

Oral Health and Its Aetiological Role in Behçet's Disease

“…This occurs when dysbiosis of the established microbial community results in inflammation and a decrease in host pathogen resistance. Numerous microbiome studies have established the aetiopathogenesis of diseases (36,38,39,(74)(75)(76).…”

“…Elevated abundances of Dethiosulfovibrionaceae and Spirochaetaceae families, with Trepenema TG5 at genus level being found in the oral microbiome from BD patient (38). Changes in microbiome profile modifying immune responses contribute to immune dysregulation during the development and progression of the diseases (38,41,42). These studies of the salivary microbiome provide information which may assist in the development of new therapies for use in BD (15,38,(40)(41)(42) (Figure 1).…”

“…Microorganisms play a critical role in maintaining the balance of health and disease as commensal microorganisms protect the mucosal barrier and prevent pathogenic colonisation ( 38 – 42 ). Although the oral mucosa is an effective physical barrier for microorganisms and their antigens ( 27 ), molecular mimicry and cross-reactivity between tissue antigens, microbial antigens and immune dysregulation can trigger oral ulcer activity in BD ( 10 , 11 , 27 , 43 ).…”