Aim: To investigate the functional effects of AIEC infection on autophagy and apoptosis responses and microbiota composition in an experimental model and IECs.
Methods: Streptomycin-treated mice were orally gavaged with 1x108AIEC-HM605 challenged with 2.5%DSS or non-DSS-treatment for 3 days. Colons from these mice and IECs infected with HM605 were assayed for the expression of cytokine, apoptosis and autophagy genes by qRT-PCR and western blot. Analysis on fecal bacterial composition was performed using 16S rRNA amplicon pyrosequencing technology.
Results: HM605 colonised the cecum and colons, induced a significantly higher in vivo permeability and expression of apoptosis and autophagy genes in the colons but did not induce colitis in non-DSS challenged mice. In contrast, HM605-infected and DSS-challenged mice presented significant symptoms of colitis, increased colonic IL-6 and mKC/CXCL1 levels and dysregulated expression of autophagy and apoptosis genes, and an imbalance in fecal Proteobacteria and Bacteriodetes spp, when compared to non-infected DSS-treated mice. HM605-infection of IECs induced significantly higher secretion of IL-8 and CCL20 levels, mounted a PI3K/AKT-dependent-mTOR/MAPK-independent autophagy response, and presented an imbalance in autophagy and apoptotic gene expression accompanied by a reduction in anti-CD95-induced caspase-3/-7 apoptosis.
Conclusions: The collected data reveal new insights into AIEC survival mechanisms in the host and on effects on microbial composition providing a plausible explanation of AIEC contribution to CD-pathophysiology.