Bowel Preparation-Induced Changes in the Gut Environment Facilitate Pathogen and Pathobiont Colonization

Bowel preparation is a common procedure performed millions of times each year to clear the intestinal tract ahead of colonoscopy. During this procedure, a laxative is administered to clear the intestinal contents, which also results in the removal of the mucus layer that normally protects the underlying epithelium. While bowel preparation is generally considered safe in healthy individuals, with the microbiota typically recovering fully, it remains unclear whether pathogenic bacteria can exploit the environmental changes induced by this procedure to cause disease. In this study, we investigated the impact of bowel preparation on the susceptibility of mice to oral infection by the bacterial pathogen Salmonella enterica serovar Typhimurium. We found that post-bowel preparation, in the absence of antibiotic treatment, Salmonella robustly colonized, expanded in the gut and translocated to extraintestinal organs, while vehicle-treated mice were protected from infection. Colonization was effective at doses as low as 1,000 CFU and was independent of Salmonella motility, indicating that bowel preparation disrupts intestinal colonization resistance against this common enteric pathogen. We also discovered that pathobionts common in patients with inflammatory bowel disease (IBD) are highly resistant to osmotic perturbation, suggesting they may take advantage of bowel preparation to expand. In a human IBD microbiota mouse model, resident pathobionts translocated to extraintestinal organs post-bowel preparation, whereas this was not seen in mice with a conventional or healthy human microbiota. These results reveal the ability of pathogens and pathobionts to exploit disruptions in the gut environment and further elucidate the importance of the mucus layer and commensal microbiota in preventing enteric pathogen infection.