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Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model
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 i...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230837/ https://www.ncbi.nlm.nih.gov/pubmed/34208228 http://dx.doi.org/10.3390/metabo11060380 |
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author | Karpe, Avinash V. Hutton, Melanie L. Mileto, Steven J. James, Meagan L. Evans, Chris Shah, Rohan M. Ghodke, Amol B. Hillyer, Katie E. Metcalfe, Suzanne S. Liu, Jian-Wei Walsh, Tom Lyras, Dena Palombo, Enzo A. Beale, David J. |
author_facet | Karpe, Avinash V. Hutton, Melanie L. Mileto, Steven J. James, Meagan L. Evans, Chris Shah, Rohan M. Ghodke, Amol B. Hillyer, Katie E. Metcalfe, Suzanne S. Liu, Jian-Wei Walsh, Tom Lyras, Dena Palombo, Enzo A. Beale, David J. |
author_sort | Karpe, Avinash V. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8230837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82308372021-06-26 Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model Karpe, Avinash V. Hutton, Melanie L. Mileto, Steven J. James, Meagan L. Evans, Chris Shah, Rohan M. Ghodke, Amol B. Hillyer, Katie E. Metcalfe, Suzanne S. Liu, Jian-Wei Walsh, Tom Lyras, Dena Palombo, Enzo A. Beale, David J. Metabolites Article 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. MDPI 2021-06-11 /pmc/articles/PMC8230837/ /pubmed/34208228 http://dx.doi.org/10.3390/metabo11060380 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Karpe, Avinash V. Hutton, Melanie L. Mileto, Steven J. James, Meagan L. Evans, Chris Shah, Rohan M. Ghodke, Amol B. Hillyer, Katie E. Metcalfe, Suzanne S. Liu, Jian-Wei Walsh, Tom Lyras, Dena Palombo, Enzo A. Beale, David J. Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model |
title | Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model |
title_full | Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model |
title_fullStr | Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model |
title_full_unstemmed | Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model |
title_short | Cryptosporidiosis Modulates the Gut Microbiome and Metabolism in a Murine Infection Model |
title_sort | cryptosporidiosis modulates the gut microbiome and metabolism in a murine infection model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230837/ https://www.ncbi.nlm.nih.gov/pubmed/34208228 http://dx.doi.org/10.3390/metabo11060380 |
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