Comparison of intestinal, oral, skin and eye microbiomes in patients with Behçet's disease

Introduction Behçet disease (BD) is a chronic inflammatory disorder with multisystemic involvement. Various factors have been implicated in its pathogenesis, including dysregulation of both the innate and adaptive immune systems. Moreover, alterations in microbiota composition across different body sites have been associated with several chronic diseases, including BD. The aim of our study was to investigate microbiota changes in skin, fecal, oral, and ocular samples of BD patients during both attack and remission phases. Materials and Methods A total of 20 patients diagnosed with Behçet disease were included in this longitudinal follow-up study, conducted over a period of two years. Patients were monitored during both attack and remission periods. Demographic data and clinical findings were collected throughout the study. For microbiota analysis, samples were obtained from the antecubital and popliteal fossae (skin), feces, oral cavity, and conjunctival surfaces (eye). DNA was extracted from all samples, and 16S rRNA gene amplification was performed using V1–V9 primers, followed by sequencing. Microbial diversity was assessed using alpha and beta diversity indices, and taxonomic composition was evaluated through relative abundance analysis. Results In fecal samples, a statistically significant increase in the Firmicutes to Bacteroidetes ratio was observed during the attack phase (77% vs 84% for Firmicutes, and 19% vs 4% for Bacteroidetes), indicating gastrointestinal dysbiosis. At the species level, Faecalibacterium prausnitzii —a beneficial butyrate-producing bacterium—was reduced in attack samples (3% vs 14%). At the genus level, Catenibacterium was more abundant in remission samples (32% vs 23%), while Collinsella was relatively higher in attack (10% vs 7%). Regarding the skin microbiome, at the genus level, Staphylococcus was the most dominant taxon in both control and attack samples; however, its abundance was lower in the attack group (53.0%) compared to controls (62.0%). Similarly, Cutibacterium was reduced in the attack samples (2.1%) compared to controls (4.5%). In contrast, Staphylococcus was more abundant in attack samples than in remission (45% vs 27%). In the oral microbiota, dominant genera included Streptococcus, Haemophilus and Veillonella. A notable decrease in Haemophilus was found during attacks (3% vs 12%), while Prevotella was relatively increased in remission samples. In eye samples, Staphylococcus and Corynebacterium were less abundant in the attack group (9% vs 21% and 12% vs 19%, respectively). Conversely, Pseudomonas was markedly higher in the attack group (69% vs 39%). At the species level, Pseudomonas aeruginosa was significantly more abundant in attack samples. Staphylococcus epidermidis was reduced in attack (5% vs 15%), while Cutibacterium acnes remained stable (8% in both groups). In remission, Pseudomonas aeruginosa abundance decreased (60% vs 71%) and Staphylococcus capitis abundance increased (6% vs 1%). Conclusion Our study demonstrated that during the attack phase in BD patients, an increased Firmicutes to Bacteroidetes ratio in fecal samples might reflect intestinal dysbiosis. Short-chain fatty acid–producing bacteria were reduced during active disease and recovered in remission. In the skin microbiota, fluctuations in Staphylococcus suggested a disrupted cutaneous microenvironment during disease activity. In oral samples, decreased Haemophilus and increased Prevotella might reflect local mucosal dysregulation. Ocular microbiota of BD patients during attacks showed increased Pseudomonas and could be associated with ocular inflammation. Overall, our findings highlighted site-specific microbial shifts associated with disease state and suggested a potential role of microbiota in the pathophysiology of Behçet disease.