Candida tropicalis infection modulates the gut microbiome and confers enhanced susceptibility to colitis in mice.
BACKGROUND & AIMS
We previously showed that abundance of C. tropicalis is significantly greater in Crohn's disease patients compared to non-disease first-degree relatives. The aim of this study was to determine the effects and mechanisms of action of C. tropicalis infection on intestinal inflammation and injury in mice.


METHODS
C57BL/6 mice were inoculated with C. tropicalis, and colitis induced by administration of dextran sodium sulfate (DSS) in drinking water. Disease severity and intestinal permeability were subsequently evaluated by endoscopy, histology, RT-qPCR, as well as 16S rRNA and NanoString analyses.


RESULTS
Infected mice showed more severe colitis, with alterations in gut mucosal Th1 and Th17 cytokine expression, and an increased frequency of mesenteric lymph node (MLN)-derived group 2 innate lymphoid cells (ILC2s) compared to uninfected controls. Gut microbiome composition, including changes in the mucin-degrading bacteria, A. Muciniphila and R. Gnavus, was significantly altered, as was expression of several genes affecting intestinal epithelial homeostasis in isolated colonoids, after C. tropicalis infection compared to uninfected controls. In line with these findings, fecal microbiome transplantation (FMT) of germ-free (GF) recipient mice using infected vs. uninfected donors exhibited altered expression of several tight-junction proteins and increased susceptibility to DSS-induced colitis.


CONCLUSIONS
C. tropicalis induces dysbiosis that involves changes in the presence of mucin-degrading bacteria, leading to altered tight junction protein expression with increased intestinal permeability and followed by induction of robust Th1/Th17 responses, which ultimately lead to an accelerated pro-inflammatory phenotype in experimental colitic mice.
['Di Martino|Luca|L|', 'De Salvo|Carlo|C|', 'Buela|Kristine-Ann|KA|', 'Hager|Christopher|C|', 'Ghannoum|Mahmoud|M|', 'Osme|Abdullah|A|', 'Buttò|Ludovica|L|', 'Bamias|Giorgos|G|', 'Pizarro|Theresa T|TT|', 'Cominelli|Fabio|F|']
colitis C. tropicalis A. muciniphila mycobiome