Candida tropicalis Infection Modulates the Gut Microbiome and Confers Enhanced Susceptibility to Colitis in Mice

Autor: Luca Di Martino, Carlo De Salvo, Kristine-Ann Buela, Christopher Hager, Mahmoud Ghannoum, Abdullah Osme, Ludovica Buttò, Giorgos Bamias, Theresa T. Pizarro, Fabio Cominelli
Rok vydání: 2021
Předmět:
C tropicalis
A muciniphila
PBS
phosphate-buffered saline
RC799-869
Th
helper T cell
CARD9
caspase-associated recruitment domain adaptor 9
Mice
RT
reverse-transcription
Cldn
claudin
MLN
mesenteric lymph node
CD
Crohn’s disease
Animals
Humans
IFN
interferon
Candida tropicalis
Lymphocytes
DSS
dextran sodium sulfate
RFU
relative fluorescence unit
CWRU
Case Western Reserve University
Original Research
T-bet+
_
TNF
tumor necrosis factor
Hepatology
IBD
inflammatory bowel disease
FMT
fecal microbiome transplantation
RORγT+
__
Dextran Sulfate
Gastroenterology
ILC
innate lymphoid cell
Diseases of the digestive system. Gastroenterology
Colitis
Immunity
Innate
B6
C57BL/6
CFU
colony forming unit
Gastrointestinal Microbiome
IL
interleukin
Mice
Inbred C57BL
rRNA
ribosomal RNA
GF
germ-free
UC
ulcerative colitis
IEBD
intestinal epithelial barrier dysfunction
qPCR
quantitative polymerase chain reaction
FITC
fluorescein isothiocyanate
Mycobiome
Zdroj: Cellular and Molecular Gastroenterology and Hepatology
Cellular and Molecular Gastroenterology and Hepatology, Vol 13, Iss 3, Pp 901-923 (2022)
ISSN: 2352-345X
Popis: 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.
Graphical abstract
Databáze: OpenAIRE
Externí odkaz: