Centre for Oral Immunobiology and Regenerative Medicine (COIRM), Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
London Behçet's Centre, Royal London Hospital, Barts Health London, UK.
Clin Immunol. 2023 Aug;253:109654. doi: 10.1016/j.clim.2023.109654. Epub 2023 May 29.
Almost 90% of Behçet's patients present with oral and/or genital ulcers which influence the disease outcome. We hypothesised that the dysregulation of the oral and genital microbiome, coupled with dysregulation of the immune response, contributes to the aetiopathogenesis of Behçet's Disease (BD) and drives disease activation.
152 BD patient samples; 70 matched oral and genital samples plus 12 unmatched samples (Female: Male, 58:12; mean age, 42 ± 13.9: 39.3 ± 10.3) to profile microbial community high-throughput sequencing of the microbiome using 16 s rRNA sequencing targeting the V1/V2 and V3/V4 hyper variable regions were used and results reviewed in relation to disease severity, Work and Social Adjustment Scale (WSAS) outcomes and medication.
Alpha and beta diversity were significantly decreased in genital compared to oral samples; p value<0.05. However, grouping the samples as to whether ulceration was present was not significant. Escherichia-Shigella was the only Amplicon Sequence Variants (ASVs) in the V1/V2 region that was shared between the oral mucosa with ulcer (O_U) and genital mucosa with ulcer (G_U) groups. This was in contrast to the V3/V4 region which indicated that Lachnospiraceae, Saccharimonadales, and Coriobacteriales were shared between the O_U and G_U groups. In addition, gender had no impact on the bacterial abundance in V1/V2 analysis of the oral and genital samples. V3/V4 analysis of genital samples demonstrated that Lactobacilli and Gardnerella were significantly increased in females (20 times) compared to the males in samples; p-adj <0.05. Interestingly in BD patients, Rothia which is commonly found in the mouth was present in both oral and genital samples. Streptococci were significantly increased while Veillonella significantly decreased in the presence of oral ulceration in the BD cohort. The clinical phenotype had no effect on V1/V2 and V3/V4 on the bacterial abundance of oral samples. However, medication e.g. colchicine had a significant effect on the oral microbial abundance (V1/V2; P = 0.020, V3/V4; P = 0.003). There was no relationship between colchicine and the presence/absence of genital ulcers. BD patients with active disease had higher WSAS scores, and their bacterial abundance differed significantly from the non-active BD patients (ADONIS, R2 = 0.05, p value =0.029).
The presence of the microbes Streptococcus, Veillonella, Gardnerella, Lactobacillus, Atopobium, Peptoniphilus, Corynebacterium and Staphylococcus may provide early evidence of BD patients are with active disease.
探讨口腔和/或生殖器溃疡是否影响白塞病（BD）的疾病结局。方法：选取 152 例 BD 患者的样本，包括 70 例口腔和生殖器匹配样本和 12 例不匹配样本（女性：男性，58：12；平均年龄，42±13.9：39.3±10.3），对微生物组进行高通量测序，采用 16s rRNA 测序靶向 V1/V2 和 V3/V4 高变区。结果：与口腔样本相比，生殖器样本的 alpha 和 beta 多样性显著降低（p 值<0.05）。然而，将样本按照是否存在溃疡进行分组并没有显著差异。在 V1/V2 区域中，Escherichia-Shigella 是唯一存在于口腔黏膜溃疡（O_U）和生殖器黏膜溃疡（G_U）组之间的扩增子序列变异（ASVs）。这与 V3/V4 区域形成对比，表明 Lachnospiraceae、Saccharimonadales 和 Coriobacteriales 存在于 O_U 和 G_U 组之间。此外，性别对口腔和生殖器样本 V1/V2 分析的细菌丰度没有影响。V3/V4 分析表明，在女性（20 倍）的生殖器样本中，乳酸杆菌和加德纳菌显著增加（p 调整值<0.05）。有趣的是，在 BD 患者中，常见于口腔的 Rothia 存在于口腔和生殖器样本中。在 BD 患者中，口腔溃疡时，链球菌显著增加，而韦荣球菌显著减少。口腔样本的临床表型对 V1/V2 和 V3/V4 的细菌丰度没有影响。然而，药物（如秋水仙碱）对口腔微生物丰度有显著影响（V1/V2；P=0.020，V3/V4；P=0.003）。秋水仙碱与生殖器溃疡的存在/不存在之间没有关系。活动期 BD 患者的 WSAS 评分较高，其细菌丰度与非活动期 BD 患者有显著差异（ADONIS，R2=0.05，p 值=0.029）。结论：微生物链球菌、韦荣球菌、乳酸杆菌、加德纳菌、Atopobium、Peptoniphilus、棒状杆菌和葡萄球菌的存在可能为 BD 患者处于活动期提供早期证据。
