Imperial College London
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Dr Julie McDonald

Faculty of Natural Sciences, Department of Life Sciences

Lecturer (MRC-CMBI)
 
 
 
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Contact

 

+44 (0)20 7594 5247julie.mcdonald Website

 
 
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Location

 

1.44Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Letertre:2020:10.1021/acs.jproteome.0c00230,
author = {Letertre, MPM and Munjoma, NC and Wolfer, K and Pechlivanis, A and McDonald, J and Hardwick, RN and Cherrington, NJ and Coen, M and Nicholson, J and Hoyles, L and Swann, J and Wilson, I},
doi = {10.1021/acs.jproteome.0c00230},
journal = {Journal of Proteome Research},
pages = {3326--3339},
title = {A two-way interaction between methotrexate and the gut microbiota of male Sprague Dawley rats},
url = {http://dx.doi.org/10.1021/acs.jproteome.0c00230},
volume = {19},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Methotrexate (MTX) is a chemotherapeutic agent that cancause a range of toxic side effects including gastrointestinal damage,hepatotoxicity, myelosuppression, and nephrotoxicity and has potentiallycomplex interactions with the gut microbiome. Following untargeted UPLCqtof-MS analysis of urine and fecal samples from male Sprague−Dawley ratsadministered at either 0, 10, 40, or 100 mg/kg of MTX, dose-dependentchanges in the endogenous metabolite profiles were detected. Semiquantitativetargeted UPLC-MS detected MTX excreted in urine as well as MTX and twometabolites, 2,4-diamino-N-10-methylpteroic acid (DAMPA) and 7-hydroxyMTX, in the feces. DAMPA is produced by the bacterial enzymecarboxypeptidase glutamate 2 (CPDG2) in the gut. Microbiota profiling(16S rRNA gene amplicon sequencing) of fecal samples showed an increase inthe relative abundance of Firmicutes over the Bacteroidetes at low doses ofMTX but the reverse at high doses. Firmicutes relative abundance was positively correlated with DAMPA excretion in feces at 48 h,which were both lower at 100 mg/kg compared to that seen at 40 mg/kg. Overall, chronic exposure to MTX appears to inducecommunity and functionality changes in the intestinal microbiota, inducing downstream perturbations in CPDG2 activity, and thusmay delay MTX detoxication to DAMPA. This reduction in metabolic clearance might be associated with increased gastrointestinaltoxicity.
AU  - Letertre,MPM
AU  - Munjoma,NC
AU  - Wolfer,K
AU  - Pechlivanis,A
AU  - McDonald,J
AU  - Hardwick,RN
AU  - Cherrington,NJ
AU  - Coen,M
AU  - Nicholson,J
AU  - Hoyles,L
AU  - Swann,J
AU  - Wilson,I
DO  - 10.1021/acs.jproteome.0c00230
EP  - 3339
PY  - 2020///
SN  - 1535-3893
SP  - 3326
TI  - A two-way interaction between methotrexate and the gut microbiota of male Sprague Dawley rats
T2  - Journal of Proteome Research
UR  - http://dx.doi.org/10.1021/acs.jproteome.0c00230
UR  - https://pubs.acs.org/doi/10.1021/acs.jproteome.0c00230
UR  - http://hdl.handle.net/10044/1/82133
VL  - 19
ER  -
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