Candida tropicalis-derived vitamin B3 exerts protective effects against intestinal inflammation by promoting IL-17A/IL-22-dependent epithelial barrier function
Journal
Gut Microbes
Journal Volume
16
Journal Issue
1
ISSN
1949-0976
1949-0984
Date Issued
2024-10-27
Author(s)
Ha T Doan
Li-Chieh Cheng
Yi-Ling Chiu
Yuan-Kai Cheng
Hsiu-Jung Lo
Abstract
Candida tropicalis-a prevalent gut commensal fungus in healthy individuals–contributes to intestinal health and disease. However, how commensal C. tropicalis influences intestinal homeostasis and barrier function is poorly understood. Here, we demonstrated that the reference strain of C. tropicalis (MYA-3404) ameliorated intestinal inflammation in murine models of chemically induced colitis and bacterial infection. Intestinal colonization of C. tropicalis robustly upregulated the expression of IL-17A and IL-22 to increase barrier function and promote proliferation of intestinal epithelial cells in the mouse colon. Metabolomics analysis of fecal samples from mice colonized with C. tropicalis revealed alterations in vitamin B3 metabolism, promoting conversion of nicotinamide to nicotinic acid. Although nicotinamide worsened colitis, treatment with nicotinic acid alleviated disease symptoms and enhanced epithelial proliferation and Th17 cell differentiation. Oral gavage of C. tropicalis mitigated nicotinamide-induced intestinal dysfunction in experimental colitis. Blockade of nicotinic acid production with nicotinamidase inhibitors lowered the protective effects against colitis in mice treated with C. tropicalis. Notably, a clinical C. tropicalis strain isolated from patients with candidemia lacked the protective effects against murine colitis observed with the reference strain. Together, our results highlight a novel role for C. tropicalis in resolving intestinal inflammation through the modulation of vitamin B3 metabolism.
Subjects
Candida tropicalis
epithelial barrier function
epithelial cell proliferation
IL-17A
IL-22
inflammatory bowel disease
mucosal immunity
vitamin B3
SDGs
Publisher
Informa UK Limited
Description
Article number 2416922
Type
journal article