Gut metabolites influence susceptibility of neonatal mice to cryptosporidiosis

Abstract

The protozoan parasite Cryptosporidium is a leading cause of diarrheal disease in those with compromised or under-developed immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection, and then tested the isolated effects of these metabolites on C. parvum invasion and growth. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, while long-chain unsaturated fatty acids enhance C. parvum invasion. The influence of these two classes of metabolites on C. parvum infection likely reflects the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Hence, gut metabolites, either from diet or produced by the microbiota, play an important role in the early susceptibility to cryptosporidiosis seen in young animals.