Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cryptosporidiosis Modulates the Gut Microbiome Metabolism and Immune Response in an Infected Host

Version 1 : Received: 19 April 2021 / Approved: 20 April 2021 / Online: 20 April 2021 (11:12:14 CEST)

A peer-reviewed article of this Preprint also exists.

Karpe, A.V.; Hutton, M.L.; Mileto, S.J.; James, M.L.; Evans, C.; Shah, R.M.; Ghodke, A.B.; Hillyer, K.E.; Metcalfe, S.S.; Liu, J.-W.; Walsh, T.; Lyras, D.; Palombo, E.A.; Beale, D.J. Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model. Metabolites 2021, 11, 380. Karpe, A.V.; Hutton, M.L.; Mileto, S.J.; James, M.L.; Evans, C.; Shah, R.M.; Ghodke, A.B.; Hillyer, K.E.; Metcalfe, S.S.; Liu, J.-W.; Walsh, T.; Lyras, D.; Palombo, E.A.; Beale, D.J. Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model. Metabolites 2021, 11, 380.

Journal reference: Metabolites 2021, 11, 380
DOI: 10.3390/metabo11060380

Abstract

Cryptosporidiosis is a major human health concern globally. Despite well-established methods, misdiagnosis remains common. Our understanding of the cryptosporidiosis biochemical mechanism remains limited, compounding the difficulty of clinical diagnosis. Here, we used a systems biology approach to investigate the underlying biochemical interactions in C57BL/6J mice infected with Cryptosporidium parvum. Faecal samples were collected daily following infection. Blood, liver tissues and luminal contents were collected 10 days post infection (dpi). High-resolution liquid chromatography and low-resolution gas chromatography coupled with mass spectrometry were used to analyse the proteomes and metabolomes of these samples. Faeces and luminal contents were additionally subjected to 16S rRNA gene sequencing. Univariate and multivariate statistical analysis of the acquired data illustrated altered host and microbial energy pathways during infection. Glycolysis/citrate cycle metabolites were depleted, while short-chain fatty acids and D-amino acids accumulated. An increased abundance of bacteria associated with a stressed gut environment was seen. Host proteins involved in energy pathways and Lactobacillus glyceraldehyde-3-phosphate dehydrogenase were upregulated during cryptosporidiosis. Liver oxalate also increased during infection. Microbiome-parasite relationships were observed to be more influential than the host-parasite association in mediating major biochemical changes in the mouse gut during cryptosporidiosis. Defining this parasite-microbiome interaction is the first step towards building a comprehensive cryptosporidiosis model towards biomarker discovery, and rapid and accurate diagnostics.

Subject Areas

Interactomics; host-parasite-microbiome relationships; extra-intestinal effects; D-amino ac-id/SCFA-induced modulation; Yeast ubiquinone salvation.

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