LAUSR

Supplemental Digital Content is available in the text ABSTRACT Objectives: Host-microbial relationship is disrupted in inflammatory bowel diseases (IBD). We hypothesized that altered gut luminal microenvironment can impact microbial virulence in IBD, leading to disruption of homeostasis and disease. We investigated the relationship between gut microenvironment and microbial virulence. Methods: Intestinal aspirates were collected from 10 non-IBD controls, 9 Crohn disease, and 10 ulcerative colitis paediatric patients during endoscopy. In vitro invasion of bacteria isolated from the duodenum and terminal ileum (TI) was quantified using gentamicin protection assays. Intestinal epithelial cells were infected in vitro by known Escherichia coli strains with patient intestinal aspirates added. Nuclear magnetic resonance spectroscopy (NMR) analysis was conducted on intestinal aspirates to identify metabolites associated with invasion; these metabolites were then introduced to the infection model. Results: There was no difference in in vitro invasion of bacteria obtained from intestinal aspirates of non-IBD and IBD patients. Incubation of laboratory E coli strains with TI aspirates from IBD patients increased their invasion into epithelial cells in vitro. NMR analysis revealed intestinal metabolites that correlated with bacterial invasion; succinate present in the intestinal aspirates correlated positively, whereas acetate and formate related negatively with invasion. Addition of exogenous succinate increased invasion of E coli in vitro. Conclusions: Alterations in the gut microenvironment in IBD can affect bacterial invasion. Succinate is associated with increased bacterial invasion and can alter bacterial virulence in IBD. This highlights the interaction between specific metabolites and bacteria that could be instrumental in propagating or suppressing inflammation in paediatric IBD patients.