抗生素诱导的肠道菌群失调对小鼠肺部真菌感染的影响及作用机制OA

Objective To explore the effect of antibiotic-induced intestinal flora dysregulation on pulmonary fungal infection and its underlying mechanism.Methods A total of 96 female C57BL/6J mice were divided into four groups:SCS:cefoperazone(-)+cyclo-phosphamide(+)+Aspergillus fumigatus(-);CCS:cefoperazone(+)+cyclophosphamide(+)+Aspergillus fumigatus(-);SCA:cefoperazone(-)+cyclophosphamide(+)+Aspergillus fumigatus(+);CCA:cefoperazone(+)+cyclophosphamide(+)+Aspergillus fumigatus(+).The 7-day survival rate,body weight,and fecal characteristics were assessed.Alterations in gut microbiota were analyzed,eosinophils in the peripheral blood and bronchoalveolar lavage fluid(BALF)were counted,histopathological examinations of the lungs and small intestine tissues were performed,and the expression of Fractalkine and CX3CR1 mRNA was analyzed.Results Compared to the SCS group,mice in the CCS group exhibited changes in gut microbiota composition and a reduction in microbial diversity.Compared to the other three groups,mice in the CCA group exhibited lethargy,reduced activity,decreased appetite,severe diarrhea,and a significantly lower 7-day survival rate(P<0.05).HE staining revealed typical inflammatory responses in the lungs and small intestine tissues of mice in the CCA group.The EOS counts increased in the blood and BALF of mice in the CCS and CCA groups(all P<0.05).Compared to the SCS group,mice in the CCS group exhibited significantly higher expression of Fractalkine and CX3CR1 mRNA in the lung and small intestine tissues(P<0.05).Conclusion Antibiotic-induced intestinal flora dysregulation exacerbated lung inflammatory responses in Aspergillus-infected mice and reduced survival rates.EOS,Fractalkine,and CX3CR1 may be involved in fungal immunity in the lungs.