Dysregulation of cholesterol and bile acid homeostasis across the gut-liver axis following Cryptosporidium intestinal infection

Cryptosporidium spp., an apicomplexan protozoan, is one of the most common pathogens responsible for moderate-to-severe diarrhea in children under 2-year-old and an important opportunistic pathogen for patients with AIDS. There are no effective vaccines and therapy available. Infection in children is associated with malnutrition, growth defect and even impaired cognitive development but underlying mechanisms remain unclear. We report here that C. parvum infection in neonatal mice impairs bile acid reabsorption in the ileum and disturbs lipid metabolism in the liver and bile acid homeostasis in the enterohepatic circulation. Reduction of bile acid pool further impairs lipid absorption in the small intestine. Moreover, replenishing bile prevents decrease of lipid absorption in the infected neonatal mice. Strikingly, bile gavage significantly reduces the infection burden and ameliorates the dysregulated homeostasis of cell proliferation and migration in intestinal epithelium following infection. These findings may guide novel therapeutic approaches for cryptosporidiosis.