Specific pathway abundances of the neonatal calf faecal microbiome are associated with susceptibility to Cryptosporidium parvum infection

Cryptosporidium parvum is a major cause of calf scour worldwide. Though therapeutic options and research are limited, it is important to understand the biology of this protozoan parasite in order to develop novel treatments against infection. The age-dependent nature of symptomatic cryptosporidiosis suggests a correlation with the undeveloped microbiome, intestinal epithelium, and immune response. This led us to hypothesise that specific taxonomic and functional features of the microbiome could predict calf susceptibility to cryptosporidiosis. In this study, faecal samples were collected from 346 ≤1-week-old calves. A case-control approach was taken whereby, 60 calves were selected, 30 of which went on to develop C. parvum infection and 30 that remained healthy, following sampling. DNA extracted from the samples underwent shotgun metagenomic sequencing. Analyses showed that functional pathways related to isoprenoid precursor biosynthesis (MEP), haem biosynthesis, and purine salvage, were significantly more abundant in calves that went on to develop diarrhoea and test positive for C. parvum compared to healthy controls. Remarkably, C. parvum lacks most of these pathways or is not solely reliant upon them. However, C. parvum still encodes enzymes for essential downstream processes which require the metabolites generated by these pathways, showing that C. parvum may scavenge those products from an external source. The host has previously been put forward as the source of these metabolites, but our study suggests that C. parvum may also be able to harness specific pathways of the microbiota in order to survive and replicate.