Increased urinary trimethylamine N-oxide following cryptosporidium infection and protein malnutrition independent of microbiome effects
Increased urinary trimethylamine N-oxide following cryptosporidium infection and protein malnutrition independent of microbiome effects
Cryptosporidium infections have been associated with growth stunting, even in the absence of diarrhea. Having previously detailed the effects of protein deficiency on both microbiome and metabolome in this model, we now describe the specific gut microbial and biochemical effects of Cryptosporidium infection. Protein-deficient mice were infected with Cryptosporidium parvum oocysts for 6-13 days and compared with uninfected controls. Following infection, there was an increase in the urinary excretion of choline- and amino-acid-derived metabolites. Conversely, infection reduced the excretion of the microbial-host cometabolite (3-hydroxyphenyl)propionate-sulfate and disrupted metabolites involved in the tricarboxylic acid (TCA) cycle. Correlation analysis of microbial and biochemical profiles resulted in associations between various microbiota members and TCA cycle metabolites, as well as some microbial-specific degradation products. However, no correlation was observed between the majority of the infection-associated metabolites and the fecal bacteria, suggesting that these biochemical perturbations are independent of concurrent changes in the relative abundance of members of the microbiota. We conclude that cryptosporidial infection in protein-deficient mice can mimic some metabolic changes seen in malnourished children and may help elucidate our understanding of long-term metabolic consequences of early childhood enteric infections.
Animals, Biomarkers/urine, Citric Acid Cycle, Cryptosporidiosis/diagnosis, Cryptosporidium parvum/isolation & purification, Feces/microbiology, Gastrointestinal Microbiome, Lipocalin-2/genetics, Male, Metabolome, Methylamines/urine, Mice, Mice, Inbred Strains, Peroxidase/genetics, Protein-Energy Malnutrition/microbiology, Up-Regulation
64-71
Bolick, David T.
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Mayneris-Perxachs, Jordi
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Medlock, Greg L.
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Kolling, Glynis L.
502c0b3d-ac97-4850-8c38-890da2124e13
Papin, Jason A.
beec0af9-791c-4f7a-9aeb-9926049bd9d0
Swann, Jonathan R.
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Guerrant, Richard L.
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1 July 2017
Bolick, David T.
35949d76-8c51-4889-9a5e-ed52db0eca2c
Mayneris-Perxachs, Jordi
921cd6b1-1c40-4cb6-9d70-9d3c4f479a78
Medlock, Greg L.
83716fb9-9592-4be2-8df5-c185ffd4d55e
Kolling, Glynis L.
502c0b3d-ac97-4850-8c38-890da2124e13
Papin, Jason A.
beec0af9-791c-4f7a-9aeb-9926049bd9d0
Swann, Jonathan R.
7c11a66b-f4b8-4dbf-aa17-ad8b0561b85c
Guerrant, Richard L.
b8c9324a-fd9b-401e-b994-105406ee8fbd
Bolick, David T., Mayneris-Perxachs, Jordi, Medlock, Greg L., Kolling, Glynis L., Papin, Jason A., Swann, Jonathan R. and Guerrant, Richard L.
(2017)
Increased urinary trimethylamine N-oxide following cryptosporidium infection and protein malnutrition independent of microbiome effects.
The Journal of Infectious Diseases, 216 (1), .
(doi:10.1093/infdis/jix234).
Abstract
Cryptosporidium infections have been associated with growth stunting, even in the absence of diarrhea. Having previously detailed the effects of protein deficiency on both microbiome and metabolome in this model, we now describe the specific gut microbial and biochemical effects of Cryptosporidium infection. Protein-deficient mice were infected with Cryptosporidium parvum oocysts for 6-13 days and compared with uninfected controls. Following infection, there was an increase in the urinary excretion of choline- and amino-acid-derived metabolites. Conversely, infection reduced the excretion of the microbial-host cometabolite (3-hydroxyphenyl)propionate-sulfate and disrupted metabolites involved in the tricarboxylic acid (TCA) cycle. Correlation analysis of microbial and biochemical profiles resulted in associations between various microbiota members and TCA cycle metabolites, as well as some microbial-specific degradation products. However, no correlation was observed between the majority of the infection-associated metabolites and the fecal bacteria, suggesting that these biochemical perturbations are independent of concurrent changes in the relative abundance of members of the microbiota. We conclude that cryptosporidial infection in protein-deficient mice can mimic some metabolic changes seen in malnourished children and may help elucidate our understanding of long-term metabolic consequences of early childhood enteric infections.
Text
jix234
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More information
Accepted/In Press date: 15 May 2017
e-pub ahead of print date: 17 May 2017
Published date: 1 July 2017
Keywords:
Animals, Biomarkers/urine, Citric Acid Cycle, Cryptosporidiosis/diagnosis, Cryptosporidium parvum/isolation & purification, Feces/microbiology, Gastrointestinal Microbiome, Lipocalin-2/genetics, Male, Metabolome, Methylamines/urine, Mice, Mice, Inbred Strains, Peroxidase/genetics, Protein-Energy Malnutrition/microbiology, Up-Regulation
Identifiers
Local EPrints ID: 440834
URI: http://eprints.soton.ac.uk/id/eprint/440834
ISSN: 0022-1899
PURE UUID: 94c6a0c8-c9df-4e9c-ae43-22e0a27c22e2
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Date deposited: 20 May 2020 16:31
Last modified: 17 Mar 2024 04:00
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Contributors
Author:
David T. Bolick
Author:
Jordi Mayneris-Perxachs
Author:
Greg L. Medlock
Author:
Glynis L. Kolling
Author:
Jason A. Papin
Author:
Richard L. Guerrant
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