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

Abstract

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 severity of pouchitis. In the Flu and laminarin groups, the expression of interferon-γ, tumor necrosis factor-α, CARD9, and phosphorylated nuclear factor kappa-B inhibitor alpha was decreased.

CONCLUSIONS:

Patients with pouchitis had altered fungal composition. Fungal dysbiosis or recognition deficiency by the host may exacerbate experimental pouchitis. Strategies targeting commensal mycobiota may provide therapeutic potential against pouchitis, especially for antibiotic-refractory patients.

• Authors: Feng Zhu, Dengyu Feng, Chao Ding, Tenghui Zhang, Jianwei Chen, Zeqian Yu, Lei Zhao, Yi Xu, Weiming Zhu, Jianfeng Gong
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 26 Issue 12 Pg. 1831-1842 (11 19 2020) ISSN: 1536-4844 [Electronic] England
• PMID: 32608473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Dextran Sulfate

Topics

• Adult
• Animals
• Colitis, Ulcerative (chemically induced, microbiology, surgery)
• Dextran Sulfate
• Disease Models, Animal
• Dysbiosis (microbiology)
• Feces (microbiology)
• Female
• Fungi
• Gastrointestinal Microbiome
• Humans
• Male
• Middle Aged
• Pouchitis (microbiology)
• Proctocolectomy, Restorative (adverse effects)
• Rats
• Rats, Sprague-Dawley