In mouse and in vitro models, bowel preparation promotes pathogen colonization, translocation, and exacerbation of inflammation

Abstract

In the United States, an estimated 14 million colonoscopies are performed yearly, each requiring patients to undergo bowel preparation, a laxative cleansing of the intestine's luminal contents. Despite its widespread use, the effects of bowel preparation on gut physiology and susceptibility to pathogens remain poorly understood, particularly in individuals with compromised gut health. Using mouse and in vitro models, we find that bowel preparation with the laxative polyethylene glycol rapidly disrupts the gut, transiently increasing susceptibility to infection by Salmonella Typhimurium, including a non-motile mutant, and by gut pathobionts derived from ulcerative colitis microbiota. Bowel preparation also facilitates bacterial translocation to extraintestinal sites (mesenteric lymph nodes, liver, and spleen) and exacerbates inflammation in a chemically induced colitis model. Although these findings are preclinical, they suggest that bowel preparation may have underappreciated risks in vulnerable populations and warrant further clinical investigation.

Keywords: DSS; IBD; IBD mouse model; PEG; Salmonella enterica serovar Typhimurium; bowel preparation; gut microbiota; gut-on-a-chip; humanized mice; inflammatory bowel disease; osmolality; pathobionts; pathogen colonization; polyethylene glycol; translocation.