Background and aims: Gut microbial and metabolic characteristics in intestinal Behcet’s disease (BD), a condition sharing many clinical similarites with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study aimed to investigate the gut microbial and metabolic characteristics, as well as potential biomarkers in intestinal BD, comparing them with those in UC, CD, and healthy controls.
Methods: Patients with UC, CD, and intestinal BD, along with healthy volunteers undergoing diagnostic endoscopies, were enrolled. Colon tissue and stool samples were analyzed using 16S ribosomal RNA sequencing, to assess microbial diversity, taxonomic composition, and functional profiling by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). Plasma metabolomic analysis was performed using gas chromatography and ultra-performance liquid chromatography-time-of-flight mass spectrometry, and quantitative enrichment analysis (QEA) was performed.
Results: In total, 100 patients (35 UC, 30 CD, and 35 BD) and 41 healthy volunteers were enrolled. While reduced microbial diversity was observed in the colon tissues from CD patients, no such significant decrease was shown in intestinal BD. The taxonomic profile of intestinal BD exhibited a tendency similar to healthy controls compared to UC or CD. However, it displayed distinct features different from UC, CD, and healthy controls (Figure 1). Common changes across all conditions included a decrease in five beneficial bacteria producing short-chain fatty acids (Fusicatenibacter saccharivorans, Coprococcus comes, Blautia obeum, Dorea formicigenerans, and Roseburai ceciola). Additional changes in intestinal BD included a decreased abundance of Subdoligranulum variable and Blautia wexlerae, which were shared features with either UC or CD. Intestinal BD-specific alterations involved decreased abundance of certain bacteria, including Bacteroides fragilis. Metabolomic profiles of intestinal BD exhibited similarity to CD and distinction from UC and controls, revealing pronounced functional changes in energy metabolism and genetic information processing through QEA (Figure 2). These findings correlated with microbial functional analysis conducted by PICRUSt.
Conclusion: This integrative analysis unveiled both common and distinctive profiles in intestinal BD when compared to UC, CD, and controls. The study identified potential biomarkers, contributing to a deeper comprehension of the unique features in these diseases, which could serve as key elements for elucidating their pathogenesis.

Figure 1. Microbial taxonomic biomarkers of IBD and intestinal BD. Genus <i>Fusicatenibacter</i>, species <i>Fusicatenibacter saccharivorans, Coprococcus comes, Blautia obeum</i>, <i>Dorea formicigenerans, </i>and<i> Roseburia ceciola</i> consistently exhibited decreased abundance, indicating their 'protective' role in UC, CD, and intestinal BD. Intestinal BD displayed fewer significant changes, mainly characterized by a decrease in the abundance of several taxa. IBD: inflammatory bowel disease, UC: ulcerative colitis, CD: Crohn’s disease, BD: Behçet’s disease

Figure 1. Microbial taxonomic biomarkers of IBD and intestinal BD. Genus Fusicatenibacter, species Fusicatenibacter saccharivorans, Coprococcus comes, Blautia obeum, Dorea formicigenerans, and Roseburia ceciola consistently exhibited decreased abundance, indicating their 'protective' role in UC, CD, and intestinal BD. Intestinal BD displayed fewer significant changes, mainly characterized by a decrease in the abundance of several taxa. IBD: inflammatory bowel disease, UC: ulcerative colitis, CD: Crohn’s disease, BD: Behçet’s disease

Figure 2. Quantitative enrichment analysis (QEA) in intestinal BD compared with control mapped to KEGG pathway (FDR adjusted<i> p</i> < 0.1). IBD: inflammatory bowel disease, UC: ulcerative colitis, CD: Crohn’s disease, BD: iBehçet’s disease, KEGG: Kyoto Encyclopedia of Genes and Genomes, FDR: false discovery rate

Figure 2. Quantitative enrichment analysis (QEA) in intestinal BD compared with control mapped to KEGG pathway (FDR adjusted p < 0.1). IBD: inflammatory bowel disease, UC: ulcerative colitis, CD: Crohn’s disease, BD: iBehçet’s disease, KEGG: Kyoto Encyclopedia of Genes and Genomes, FDR: false discovery rate

Jae Hee Cheon

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