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

Cryptosporidium spp., an apicomplexan protozoan, is one of the most common pathogens causing moderate-to-severe diarrhea in children under 2 years of age and is also an important opportunistic pathogen for patients with AIDS. There are currently no effective vaccines or therapies available. Infection in children is associated with malnutrition, growth defects, 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, disrupts lipid metabolism in the liver, and alters bile acid homeostasis in the enterohepatic circulation. The reduction of bile acid pool further impairs lipid absorption in the small intestine. Additionally, replenishing bile prevents the decline in lipid absorption in 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.