Priority order of neonatal colonization by a probiotic or pathogenic Escherichia coli strain dictates the host response to experimental colitis

The alarming prevalence of inflammatory bowel disease (IBD) in early childhood is associated with imbalances in the microbiome, the immune response, and environmental factors. Some pathogenic ( strains have been found in IBD patients, where they may influence disease progression. Therefore, the discovery of new harmful bacterial strains that have the potential to drive the inflammatory response is of great importance. In this study, we compared the immunomodulatory properties of two strains of serotype O6: the probiotic Nissle 1917 and the uropathogenic O6:K13:H1. Using the epithelial Caco-2 cell line, we investigated the different abilities of the strains to adhere to and invade epithelial cells. We confirmed the potential of Nissle 1917 to modulate the Th1 immune response in a specific manner in an setting by stimulating mouse bone marrow-derived dendritic cells (BM-DCs). In gnotobiotic experiments, we demonstrated that neonatal colonization with Nissle 1917 achieves a stable high concentration in the intestine and protects mice from the progressive effect of O6:K13:H1 in developing ulcerative colitis in an experimental model. In contrast, a single-dose treatment with Nissle 1917 is ineffective in achieving such high concentrations and does not protect against DSS-induced ulcerative colitis in mice neonatally colonized with pathobiont O6:K13:H1. Despite the stable coexistence of both strains in the intestinal environment of the mice, we demonstrated a beneficial competitive interaction between the early colonizing Nissle 1917 and the late-arriving strain O6:K13:H1, suggesting its anti-inflammatory potential for the host. This study highlights the importance of the sequence of bacterial colonization, which influences the development of the immune response in the host gut and potentially impacts future quality of life.