Effects of Cryptosporidium infections on host cell metabolome and host mitochondrial associations

Cryptosporidium is an important gut microbe whose contributions towards infant and immunocompromise patient mortality rates are steadily increasing. However, current techniques for studying the parasite are few and far between, relying on a combination of in-silico predictions and medical reports. The development of an in-vitro culture system, using COLO-680N cells (derived from an esophogeal squamous cell carcinoma), has provided the Cryptosporidium community with the opportunity to expand its toolkit for investigating this disease. One area in particular that is sorely overlooked is the effect infection has on host metabolic processes, especially those of the host mitochondria, which have been shown anecdotally in previous studies as being in abundance surrounding the sites of infection. Using a 1H Nuclear Magnetic Resonance approach to metabolomics, we have explored the nature of the mouse gut metabolome as well as providing the first insight into the metabolome of an infected cell line. Through a combination of Partial Least Squares Discriminant Analysis and predictive modelling, we demonstrate new understandings of the effects of a Cryptosporidium infection, while verifying the presence of known metabolic changes. Of particular note is the potential contribution of host derived taurine to the diuretic aspects of the disease previously attributed to a solely parasite based alteration of the gut environment. This practical and informative approach can spearhead our understanding of the Cryptosporidium-host metabolic exchange and thus provide novel targets for tackling this deadly parasite.