Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model

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. 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.

Gut Microbial Perturbation and Host Response Induces Redox Pathway Upregulation along the Gut-liver Axis during Giardiasis in C57BL/6J Mouse Model

“…In this study, we showed that giardiasis results in greater expression of energy and associated pathways in the duodenumjejunum and colon. This was somewhat different to the mechanism during cryptosporidiosis, where these pathways were greatly upregulated in the jejunum-ileum [23,24]. It has been shown that the microaerophilic nature of Giardia aids in modulating the energy pathways during increased oxygen tension [12].…”

“…Microbial, protein and metabolic extractions from luminal washes, blood serum and liver were performed as per the protocols reported previously [24] without any modifications. Amplicons were generated from the V3 and V4 regions of 16S rRNA using genespecific primers.…”

Gut Fungal Microbiome Responses to Natural Cryptosporidium Infection in Horses

“…survival in the hosts’ gut must interact with intestinal constituents to compensate for deficiencies, i.e., lack of numerous metabolic systems ( Alcock et al, 2012 ). Gut microbiome–parasite relationship was demonstrated to be a medium in modulating significant biochemical changes during cryptosporidiosis ( Karpe et al, 2021 ). Charania et al (2020) identified that specific changes in the gut microbiome allow for more favorable survival of Cryptosporidium parasite in mice ( Charania et al, 2020 ), hence this conclusion supported the current results.…”

First Metabolic Insights into Ex Vivo Cryptosporidium parvum-Infected Bovine Small Intestinal Explants Studied under Physioxic Conditions

“…As previously stated, the impact of microbial consortia in the parasite-epithelial host cell interaction needs to be recognized, and more comprehensive approaches are required in order to address such complex multispecies interactions [22,75].…”