TY - JOUR
TI - Candida tropicalis Infection Modulates the Gut Microbiome and Confers
Enhanced Susceptibility to Colitis in Mice
AU - Di Martino, Luca
AU - De Salvo, Carlo
AU - Buela, Kristine-Ann
AU - Hager,
AU - Christopher
AU - Ghannoum, Mahmoud
AU - Osme, Abdullah
AU - Butto, Ludovica
AU - and Bamias, Giorgos
AU - Pizarro, Theresa T.
AU - Cominelli, Fabio
JO - CMGH Cellular and Molecular Gastroenterology and Hepatology
PY - 2022
VL - 13
TODO - 3
SP - 901-923
PB - W B SAUNDERS CO-ELSEVIER INC
SN - 2352-345X
TODO - 10.1016/j.jcmgh.2021.11.008
TODO - C tropicalis; Colitis; A muciniphila; Mycobiome
TODO - BACKGROUND & AIMS: We previously showed that abundance of Candida
tropicalis is significantly greater in Crohn’s disease patients compared
with first-degree relatives without Crohn’s disease. 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 was
induced by administration of dextran sodium sulfate in drinking water.
Disease severity and intestinal permeability subsequently were evaluated
by endoscopy, histology, quantitative reverse-transcription polymerase
chain reaction, as well as 16S ribosomal RNA and NanoString analyses
(NanoString Technologies, Seattle, WA).
RESULTS: Infected mice showed more severe colitis, with alterations in
gut mucosal helper T cells (Th)1 and Th17 cytokine expression, and an
increased frequency of mesenteric lymph node-derived group 2 innate
lymphoid cells compared with uninfected controls. Gut microbiome
composition, including changes in the mucin-degrading bacteria,
Akkermansia muciniphila and Ruminococcus gnavus, was altered
significantly, as was expression of several genes affecting intestinal
epithelial homeostasis in isolated colonoids, after C tropicalis
infection compared with uninfected controls. In line with these
findings, fecal microbiome transplantation of germ-free recipient mice
using infected vs uninfected donors showed altered expression of several
tight-junction proteins and increased susceptibility to dextran sodium
sulfate-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 proinflammatory phenotype in experimental colitic mice.
ER -