The Protective Effect And Related Mechanisms Of Intestinal Microbiota Against Invasive Candidiasis

Objective: The intestinal microbiota is closely related to the health of the host,and it has been reported to play a protective role in various diseases.It plays a vital role in human health.This study focuses on exploring the relationship between the microbiota and the host's ability to resist invasive candidiasis through a mouse model of intestinal microbiota loss.Methods: First,mice were fed with antibiotic formula water for 3weeks according to the bacterial removal method commonly used in reported studies,and intestinal microbial culture and tissue function tests were performed on antibiotic model mice and normal mice to evaluate the treatment effect and impact.Then,the antibiotic-treated(ABX)group and the conventional-housed(CNV)group(as the control group)were intravenously infected with fungi,and their different responses were observed and compared.Fecal microbiota transplantation(FMT)was applied to ABX mice to evaluate the effect of restoring intestinal microbiota on the host's resistance to invasive candidiasis.16 S ribosomal RNA gene sequencing was performed on fecal samples of uninfected ABX and CNV groups to characterize their microbial composition.Results: In our model,antibiotic treatment did not cause systemic Candida infection and histopathological damage in mice after clearingintestinal flora.Compared with the two groups of mice after infection,the response of Th17 and Th1 type cells of ABX mice was significantly reduced,and the response of Th2 type cells was significantly enhanced.Both the rcombinant IL-17 A treatment and FMT improved the survival rate of ABX mice during invasive candidiasis and increased serum IL-17 A and IFN-? levels,while recombinant IFN-? treatment did not significantly increase its survival rate.Sequencing analysis showed that the structure of intestinal microbiota in the two groups of uninfected mice was significantly different.The community diversity and richness of intestinal microbiota in ABX mice was significantly reduced,and the proportion of Proteobacteria increased and the proportion of Firmicutes decreased.Conclusions: Our research shows that the intestinal microbiota mainly plays a protective role in invasive candidiasis through Th17 response and IL-17 A,and the decreased resistance of the host to invasive candidiasis is related to to the changes in the composition of intestinal microbiota.