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Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth

The gut microbiota’s function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tum...

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Autores principales: McKee, Alastair M., Kirkup, Benjamin M., Madgwick, Matthew, Fowler, Wesley J., Price, Christopher A., Dreger, Sally A., Ansorge, Rebecca, Makin, Kate A., Caim, Shabhonam, Le Gall, Gwenaelle, Paveley, Jack, Leclaire, Charlotte, Dalby, Matthew, Alcon-Giner, Cristina, Andrusaite, Anna, Feng, Tzu-Yu, Di Modica, Martina, Triulzi, Tiziana, Tagliabue, Elda, Milling, Simon W.F., Weilbaecher, Katherine N., Rutkowski, Melanie R., Korcsmáros, Tamás, Hall, Lindsay J., Robinson, Stephen D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426205/
https://www.ncbi.nlm.nih.gov/pubmed/34522855
http://dx.doi.org/10.1016/j.isci.2021.103012
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author McKee, Alastair M.
Kirkup, Benjamin M.
Madgwick, Matthew
Fowler, Wesley J.
Price, Christopher A.
Dreger, Sally A.
Ansorge, Rebecca
Makin, Kate A.
Caim, Shabhonam
Le Gall, Gwenaelle
Paveley, Jack
Leclaire, Charlotte
Dalby, Matthew
Alcon-Giner, Cristina
Andrusaite, Anna
Feng, Tzu-Yu
Di Modica, Martina
Triulzi, Tiziana
Tagliabue, Elda
Milling, Simon W.F.
Weilbaecher, Katherine N.
Rutkowski, Melanie R.
Korcsmáros, Tamás
Hall, Lindsay J.
Robinson, Stephen D.
author_facet McKee, Alastair M.
Kirkup, Benjamin M.
Madgwick, Matthew
Fowler, Wesley J.
Price, Christopher A.
Dreger, Sally A.
Ansorge, Rebecca
Makin, Kate A.
Caim, Shabhonam
Le Gall, Gwenaelle
Paveley, Jack
Leclaire, Charlotte
Dalby, Matthew
Alcon-Giner, Cristina
Andrusaite, Anna
Feng, Tzu-Yu
Di Modica, Martina
Triulzi, Tiziana
Tagliabue, Elda
Milling, Simon W.F.
Weilbaecher, Katherine N.
Rutkowski, Melanie R.
Korcsmáros, Tamás
Hall, Lindsay J.
Robinson, Stephen D.
author_sort McKee, Alastair M.
collection PubMed
description The gut microbiota’s function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tumor progression in multiple BrCa mouse models. Metagenomics highlights the common loss of several bacterial species following antibiotic administration. One such bacteria, Faecalibaculum rodentium, rescued this increased tumor growth. Single-cell transcriptomics identified an increased number of cells with a stromal signature in tumors, and subsequent histology revealed an increased abundance of mast cells in the tumor stromal regions. We show that administration of a mast cell stabilizer, cromolyn, rescues increased tumor growth in antibiotic treated animals but has no influence on tumors from control cohorts. These findings highlight that BrCa-microbiota interactions are different from other cancers studied to date and suggest new research avenues for therapy development.
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spelling pubmed-84262052021-09-13 Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth McKee, Alastair M. Kirkup, Benjamin M. Madgwick, Matthew Fowler, Wesley J. Price, Christopher A. Dreger, Sally A. Ansorge, Rebecca Makin, Kate A. Caim, Shabhonam Le Gall, Gwenaelle Paveley, Jack Leclaire, Charlotte Dalby, Matthew Alcon-Giner, Cristina Andrusaite, Anna Feng, Tzu-Yu Di Modica, Martina Triulzi, Tiziana Tagliabue, Elda Milling, Simon W.F. Weilbaecher, Katherine N. Rutkowski, Melanie R. Korcsmáros, Tamás Hall, Lindsay J. Robinson, Stephen D. iScience Article The gut microbiota’s function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tumor progression in multiple BrCa mouse models. Metagenomics highlights the common loss of several bacterial species following antibiotic administration. One such bacteria, Faecalibaculum rodentium, rescued this increased tumor growth. Single-cell transcriptomics identified an increased number of cells with a stromal signature in tumors, and subsequent histology revealed an increased abundance of mast cells in the tumor stromal regions. We show that administration of a mast cell stabilizer, cromolyn, rescues increased tumor growth in antibiotic treated animals but has no influence on tumors from control cohorts. These findings highlight that BrCa-microbiota interactions are different from other cancers studied to date and suggest new research avenues for therapy development. Elsevier 2021-08-20 /pmc/articles/PMC8426205/ /pubmed/34522855 http://dx.doi.org/10.1016/j.isci.2021.103012 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
McKee, Alastair M.
Kirkup, Benjamin M.
Madgwick, Matthew
Fowler, Wesley J.
Price, Christopher A.
Dreger, Sally A.
Ansorge, Rebecca
Makin, Kate A.
Caim, Shabhonam
Le Gall, Gwenaelle
Paveley, Jack
Leclaire, Charlotte
Dalby, Matthew
Alcon-Giner, Cristina
Andrusaite, Anna
Feng, Tzu-Yu
Di Modica, Martina
Triulzi, Tiziana
Tagliabue, Elda
Milling, Simon W.F.
Weilbaecher, Katherine N.
Rutkowski, Melanie R.
Korcsmáros, Tamás
Hall, Lindsay J.
Robinson, Stephen D.
Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth
title Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth
title_full Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth
title_fullStr Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth
title_full_unstemmed Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth
title_short Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth
title_sort antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426205/
https://www.ncbi.nlm.nih.gov/pubmed/34522855
http://dx.doi.org/10.1016/j.isci.2021.103012
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