Abstract
BackgroundThe aetiopathogeneses of Behçet’s Disease (BD) remains elusive with multifactorial genetic and epigenetic factors resulting in multisystemic disease. Oral and genital ulceration are common and influences disease outcome. We hypothesised that dysregulation of genital and oral microbial communities contributes to BD disease activity. 153 BD patients’ samples, 70 matched oral and genital (Female: Male, 58:12; mean age, 42±13.9: 39.3±10.3), 12 unmatched samples; 16s rRNA sequencing utilised and V1/V2 and V3/V4 regions analysed. BD outcomes: oral and genital ulcer severity and BD activity scores, Psychological and Social Well-being scales, Headache Impact Test-6 (HIT-6) were included. All the analyses were performed with R software. ResultsThe alpha and beta diversity had anatomical specificity, with significant differences between genital and oral samples; p values<0.05 irrespective of presence or absence of ulcers. Interestingly, in the genital area Bacteroidota were present (G_U: 29% - 10%) and (G_nU: 27% - 14%) compared to less than 1% oral area of V1/V2 and V3/V4. Proteobacteria were uniquely present with (O_U: 9%) and (O_nU: 12%) in oral, and less than 0.01% in genital area for V3/V4 region. Gender anatomical specific communities were noted: females with genital ulcers Gardnerella, Lactobacillus, Atopobium were significantly increased compared to than males, with V3/V4 analysis indicating that Lactobacillus and Gardnerella were significantly increased by 20 times in females than males (p-adj <0.05). In contrast Peptoniphilus and Corynebacterium were significantly increased in males than females. Streptococcus was significantly increased with oral ulceration, while Veillonella was significantly decreased in patients without oral ulceration. Colchicine had a significant effect on the bacterial abundance irrespective of the presence or absence of ulceration. In this cohort, the WSAS (Work and Social Adjustment Scale) values were higher in active disease. ConclusionOur results suggest that dysregulated microbial communities occur in BD. V1/V2 demonstrates that during episodes of ulceration the pathogenic bacteria genus Escherichia-Shigella appear in both oral and genital ulcers. V3/V4 outcomes show that ulceration in both regions is assigned to genus; Lachnospiraceae, Saccharimonidales, Coriobacteriales. Streptococcus is related to the presence of oral ulcers, while Veillonella is presence when patients are ulcers free may be a useful marker of disease regression.