Distinct microbiota composition and dendritic cell activation in the appendix microenvironment of ulcerative colitis patients

Appendectomy has been associated with reduced risk of developing ulcerative colitis (UC) or experiencing flares after diagnosis, suggesting the appendix may play a role in UC pathogenesis. Given its function in microbial homeostasis and gut immunity, we investigated the relationship between mucosal microbiota and immune environment of the appendix in UC. Appendix tissue was collected from 85 patients undergoing surgery for UC, acute appendicitis (APA) or colon cancer (CC). Immunophenotyping of dendritic cells (DC), macrophages and T lymphocytes was performed using flow cytometry. Microbiota composition was analyzed via 16S rRNA gene amplicon sequencing. Although alpha diversity did not differ between UC and non-UC appendices, beta diversity indicated significant compositional differences. Five bacterial species (<i>Actinomyces hyovaginalis</i>, <i>Mogibacterium sp</i>. <i>Fusobacterium sp</i>. <i>Pseudoramibacter eubacterium</i>, and <i>Streptococcus anginosus</i>) were significantly reduced in the UC appendix compared to APA. However, no species were associated with UC disease activity. In contrast, UC patients showed a significantly higher frequency of activated DCs (CD1a⁺ HLAdr⁺ CD86⁺). DC activation levels correlated with daily stool frequency and T-cell activation. These findings suggest that the appendix may contribute to UC pathogenesis through immune, rather than microbial, mechanisms - supporting a role for dendritic cell-mediated T-cell priming in colonic inflammation.