Microbiome-Metabolomics Analysis of the Impacts of Cryptosporidium muris Infection in BALB/C Mice

Cryptosporidium is a leading cause of diarrheal disease and mortality in young children worldwide. Cryptosporidium invades small intestinal epithelial cells and forms a unique intracellular niche, a process that may alter gut microbes and their production metabolites. However, the mechanism of interactions between gut microbes, metabolites, and parasites is poorly understood. Here, we first characterized the impacts of Cryptosporidium infection on gut microbiota using a microbiome-to-metabolome association study. BALB/c mice were gavaged with Cryptosporidium muris, and fecal samples were collected at 0, 7, 14, 21, and 28 days postinfection (dpi) to observe changes in the intestinal microbes of the body during parasite infection. The infected group had a significantly increased relative abundance of bacterial taxa, such as and Prevotella ( < 0.05), associated with the biosynthesis of short-chain fatty acids (SCFAs). Metabolites related to the metabolic pathways, steroid hormone biosynthesis, and biosynthesis of unsaturated fatty acids pathway were upregulated at 7 dpi, indicating that related metabolites in the biosynthesis of unsaturated fatty acids may be essential for C. muris reproduction . The metabolites involved in metabolic pathways, bile secretion, and primary bile acid biosynthesis were upregulated at 14 dpi, and we speculate that these metabolites may be critical to the growth and development of Cryptosporidium oocysts in the host. Correlation analysis revealed that bacteria are significantly associated with α-linolenic acid metabolism pathways ( < 0.05). The gut microbiota changes dynamically, and the metabolites involved in fatty acid and bile acid biosynthesis may play important roles during cryptosporidiosis. Details of the gut microbiota and the metabolome after infection with Cryptosporidium may aid in the discovery of specific diagnostic markers and help us understand the changes in parasite metabolic pathways. Cryptosporidiosis is a gastrointestinal disease in humans and animals caused by the protozoan parasite Cryptosporidium. Control and treatment of the disease is challenging due to the lack of sensitive diagnostic tools and effective chemotherapy. The dynamics of gut microbiota and metabolites during Cryptosporidium infection may be the key to finding drugs and targets for parasite infection control. Our results indicate that C. muris infection can disrupt gut microbiota and metabolites, resulting in decreased bacterial abundance at t