Specific pathway abundances in the neonatal calf faecal microbiome are associated with susceptibility to Cryptosporidium parvum infection: a metagenomic analysis

Hares, MF ORCID: 0000-0003-4249-7628, Griffiths, BE ORCID: 0000-0002-2698-9561, Johnson, F, Nelson, C, Haldenby, S, Stewart, CJ, Duncan, JS ORCID: 0000-0002-1370-3085, Oikonomou, G ORCID: 0000-0002-4451-4199 and Coombes, JL (2023) Specific pathway abundances in the neonatal calf faecal microbiome are associated with susceptibility to Cryptosporidium parvum infection: a metagenomic analysis. Animal Microbiome, 5 (1). 43-.

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Abstract

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p><jats:italic>Cryptosporidium parvum</jats:italic> is the main cause of calf scour worldwide. With limited therapeutic options and research compared to other <jats:italic>Apicomplexa</jats:italic>, 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 that specific features of the early life microbiome could predict calf susceptibility to <jats:italic>C. parvum</jats:italic> infection.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>In this study, a single faecal swab sample was collected from each calf within the first week of life in a cohort of 346 animals. All 346 calves were subsequently monitored for clinical signs of cryptosporidiosis, and calves that developed diarrhoea were tested for <jats:italic>Rotavirus</jats:italic>, <jats:italic>Coronavirus</jats:italic>, <jats:italic>E. coli</jats:italic> F5 (K99) and <jats:italic>C. parvum</jats:italic> by lateral flow test (LFT). A retrospective case–control approach was taken whereby a subset of healthy calves (Control group; n = 33) and calves that went on to develop clinical signs of infectious diarrhoea and test positive for <jats:italic>C. parvum</jats:italic> infection via LFT (<jats:italic>Cryptosporidium</jats:italic>-positive group; n = 32) were selected from this cohort, five of which were excluded due to low DNA quality. A metagenomic analysis was conducted on the faecal microbiomes of the control group (n = 30) and the <jats:italic>Cryptosporidium</jats:italic>-positive group (n = 30) prior to infection, to determine features predictive of cryptosporidiosis. Taxonomic analysis showed no significant differences in alpha diversity, beta diversity, and taxa relative abundance between controls and <jats:italic>Cryptosporidium</jats:italic>-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 <jats:italic>C. parvum</jats:italic> (<jats:italic>q</jats:italic> ≤ 0.25). These pathways are either absent or streamlined in the <jats:italic>C. parvum</jats:italic> parasites. Though the de novo production of isoprenoid precursors, haem and purines are absent, <jats:italic>C. parvum</jats:italic> has been shown to encode enzymes that catalyse the downstream reactions of these pathway metabolites, indicating that <jats:italic>C. parvum</jats:italic> may scavenge those products from an external source.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The host has previously been put forward as the source of essential metabolites, but our study suggests that <jats:italic>C. parvum</jats:italic> 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 therapeutic targets for the prevention or mitigation of cryptosporidiosis in bovine neonates.</jats:p> </jats:sec>

Item Type:	Article
Uncontrolled Keywords:	Cryptosporidium parvum, Bovine, Cryptosporidiosis, Faecal microbiome, Metagenome, Pathway abundances, Functional profiling
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	13 Sep 2023 10:37
Last Modified:	29 Sep 2023 10:38
DOI:	10.1186/s42523-023-00265-5
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3172714