Fungal-bacterial interactions in mice with dextran sulfate sodium (DSS)-induced acute and chronic colitis

摘要

The commensal intestinal microbiota plays critical roles in the development of inflammatory bowel diseases (IBD). However, the importance of intestinal fungi and their interactions with bacteria in the pathogenesis of IBD is unclear. In this study, anti-fungal drugs (fluconazole or amphotericin B [AmpB]) were administered to control mice and those treated, acutely (A-DSS) and chronically (C-DSS) with DSS. The severity of colonic inflammation was assessed, and pro-inflammatory cytokine levels in the colonic mucosa and serum were detected by real-time PCR and multiplex ELISA assay, respectively. The colonic bacterial 16S rDNA V3 region was analysed in normal and anti-fungal drug-treated mice by pyrosequencing. Specific bacterial genera related to IBD, butyryl-CoA/acetate-CoA transferase (a key transferase for butyrate production in bacteria) and tight-junction proteins (occludin and ZO-1) in the colonic mucosa were detected by real-time PCR and/or western blot. The results showed that compared with controls, intestinal Bacteroides, Alistipes, and Lactobacillus were increased in fluconazole treated mice; while only Alistipes was increased in AmpB treated mice. Clostridium cluster XIVa and butyryl-CoA/acetate-CoA transferase levels were reduced in both groups. Treatment with a high dose of anti-fungal drugs dampened colonic occludin and ZO-1, aggravated A-DSS colitis, and exhibited no beneficial role in C-DSS colitis. However, reducing fluconazole concentration to an appropriate dose attenuated C-DSS colitis. Thus, fungi are important co-operators with bacteria in maintaining intestinal micro-ecological equilibrium. Extensive clearance of gut fungi could disrupt intestinal bacterial homeostasis and have an adverse impact on IBD. Studies on appropriate utilize of anti-fungal drugs in IBD treatment are needed.