Fungal Dysbiosis Aggravates Pouchitis in a Rat Model of Ileal Pouch Anal Anastomosis

作者：Feng Zhu, Dengyu Feng, Chao Ding, Tenghui Zhang, Jianwei Chen, Zeqian Yu, Lei Zhao, Yi Xu, Weiming Zhu, Jianfeng Gong · 发表于：Inflammatory Bowel Diseases · 年份：2020 · DOI：10.1093/ibd/izaa111 · 被引用次数：6 · 研究领域：Inflammatory Bowel Disease、Gut microbiota and health、Probiotics and Fermented Foods

BACKGROUND: Although the interaction between gut microbiota and pouchitis after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) has been confirmed, evidence of commensal mycobiota in the etiology of pouchitis is still lacking. This study aimed to investigate the role of fungi in the pathogenesis of pouchitis. METHODS: Fecal samples were collected from UC patients with or without pouchitis after IPAA. Experimental pouchitis was induced by 5% dextran sulfate sodium for 7 consecutive days in a rat model of IPAA. Fungal dysbiosis was induced by 0.5% fluconazole (Flu), and commensal fungal recognition through dectin-1 was blocked by 5% laminarin. Fecal fungal composition was analyzed using internal transcribed spacer 2 sequencing. Severity of pouchitis and activation of the CARD9-nuclear factor kappa-B pathway was determined among different groups. RESULTS: Patients with pouchitis had a lower alpha (α) diversity in mycobiota composition and a higher abundance of Saccharomyces at the genus level compared with those with a normal pouch. In the rat model of pouchitis, Flu treatment decreased fungal burden but induced fungal dysbiosis, characterized by increased α diversity, a decreased relative abundance of Kazachstania, and increased Polythrincium and Saccharomyces. In addition, Flu treatment worsened dextran sulfate sodium pouchitis, as indicated by increased mortality, weight loss, higher histological score, and CD4+ cell infiltration. Laminarin also increased the ...