Specific pathway abundances in the neonatal calf faecal microbiome are associated with susceptibility to Cryptosporidium parvum infection: A metagenomic analysis.
Cryptosporidium parvum is the main cause of calf scour globally. With limited therapeutic options and research compared to other Apicomplexa, it is important to understand the parasites' biology and interactions with the host and microbiome in order to develop novel strategies against this infection. The age-dependent nature of symptomatic cryptosporidiosis suggests a link to the undeveloped immune response, the immature intestinal epithelium and its associated microbiota. This led us to hypothesise whether specific features of the early life microbiome could predict calves' susceptibility to C. parvum infection. In this study, faecal samples were collected from =1-week-old calves (n=346). A retrospective case-control approach was taken whereby a metagenomic analysis was conducted on healthy calves (Control group; n=30) and calves that went on to develop diarrhoea and test positive for C. parvum infection (Cryptosporidium-positive group; n=30).  Taxonomic analysis showed no significant differences in alpha diversity, beta diversity and taxa relative abundance between controls and Cryptosporidium-positive groups. Analysis of functional potential showed pathways related to isoprenoid precursor, haem and purine biosynthesis were significantly higher in abundance in calves that later tested positive for C. parvum (q=0.25). These pathways are uniquely lacking in the C. parvum parasites, unlike the other Apicomplexa. Though the de novo production of isoprenoid precursors, haem and purines are absent, C. parvum has been shown to encode enzymes that catalyse the downstream reactions of these pathway metabolites, indicating that C. parvum may scavenge those products from an external source. The host has previously been put forward as the source of essential metabolites, but our study suggests that C. parvum may also be able to harness specific metabolic pathways of the microbiota in order to survive and replicate. This finding is important as components of these microbial pathways could be exploited as potential drug targets for the prevention or mitigation of cryptosporidiosis in bovine neonates.