Abstract
Cryptosporidiosis is a gastrointestinal disease in humans and animals caused by infection with the protozoan parasite Cryptosporidium. In healthy individuals, the disease manifests mainly as acute self-limiting diarrhoea, but may be chronic and life threatening for those with compromised immune systems. Control and treatment of the disease is challenged by the lack of sensitive diagnostic tools and broad-spectrum chemotherapy. Metabolomics, or metabolite profiling, is an emerging field of study, which enables characterisation of the end products of regulatory processes in a biological system. Analysis of changes in metabolite patterns reflects changes in biochemical regulation, production and control, and may contribute to understanding the effects of Cryptosporidium infection in the host environment. In the present study, metabolomic analysis of faecal samples from experimentally infected mice was carried out to assess metabolite profiles pertaining to the infection. Gas-chromatography mass spectrometry (GC-MS) carried out on faecal samples from a group of C. parvum infected mice and a group of uninfected control mice detected a mean total of 220 compounds. Multivariate analyses showed distinct differences between the profiles of C. parvum infected mice and uninfected control mice,identifying a total of 40 compounds, or metabolites that contributed most to the variance between the two groups. These metabolites consisted of amino acids (n = 17), carbohydrates (n = 8), lipids (n = 7), organic acids (n = 3) and other various metabolites (n = 5), which showed significant differences in levels of metabolite abundance between the infected and uninfected mice groups (p < 0.05). The metabolites detected in this study as well as the differences in abundance between the C. parvum infected and the uninfected control mice, highlights the effects of the infection on intestinal permeability and the fate of the metabolites as a result of nutrient scavenging by the parasite to supplement its streamlined metabolism.
Highlights
Cryptosporidiosis, a gastroenteric disease characterized mainly by diarrheal illnesses in humans and mammals is caused by infection with the protozoan parasite Cryptosporidium
Principal component analysis (PCA) of the mass spectrometry (MS) data normalised to the internal standard showed distinct clustering of the C. parvum infected mice and the uninfected control mice
Results from the present study showed that this was not the case as analyses of the faecal metabolite profiles from both Cryptosporidium infected and uninfected mice showed that lower faecal metabolite abundances were generally recorded from the infected mice compared to that of the uninfected mice
Summary
Cryptosporidiosis, a gastroenteric disease characterized mainly by diarrheal illnesses in humans and mammals is caused by infection with the protozoan parasite Cryptosporidium. The disease, though mainly self-limiting in those that are immunocompetent, can be chronic and lead to severe dehydration with terminal results in those that are immunocompromised [1]. Children, those age five years or less are most susceptible to cryptosporidiosis where chronic infections have been shown to impair growth and cognitive development. More sensitive molecular tools are available and widely used for the detection of Cryptosporidium [3], due to the costs involved, routine diagnosis of Cryptosporidium in most pathology laboratories still relies on microscopy, which lacks specificity and sensitivity, when oocyst numbers are low [5,6]
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