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Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain

Chemotherapy induced peripheral neuropathy (CIPN), a toxic side effect of some cancer treatments, negatively impacts patient outcomes and drastically reduces survivor’s quality of life (QOL). Uncovering the mechanisms driving chemotherapy-induced CIPN is urgently needed to facilitate the development...

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Autores principales: Ramakrishna, Chandran, Corleto, Jose, Ruegger, Paul M., Logan, Geoffrey D., Peacock, Beth B., Mendonca, Stacee, Yamaki, Shanni, Adamson, Trinka, Ermel, Richard, McKemy, David, Borneman, James, Cantin, Edouard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937259/
https://www.ncbi.nlm.nih.gov/pubmed/31889131
http://dx.doi.org/10.1038/s41598-019-56832-x
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author Ramakrishna, Chandran
Corleto, Jose
Ruegger, Paul M.
Logan, Geoffrey D.
Peacock, Beth B.
Mendonca, Stacee
Yamaki, Shanni
Adamson, Trinka
Ermel, Richard
McKemy, David
Borneman, James
Cantin, Edouard M.
author_facet Ramakrishna, Chandran
Corleto, Jose
Ruegger, Paul M.
Logan, Geoffrey D.
Peacock, Beth B.
Mendonca, Stacee
Yamaki, Shanni
Adamson, Trinka
Ermel, Richard
McKemy, David
Borneman, James
Cantin, Edouard M.
author_sort Ramakrishna, Chandran
collection PubMed
description Chemotherapy induced peripheral neuropathy (CIPN), a toxic side effect of some cancer treatments, negatively impacts patient outcomes and drastically reduces survivor’s quality of life (QOL). Uncovering the mechanisms driving chemotherapy-induced CIPN is urgently needed to facilitate the development of effective treatments, as currently there are none. Observing that C57BL/6 (B6) and 129SvEv (129) mice are respectively sensitive and resistant to Paclitaxel-induced pain, we investigated the involvement of the gut microbiota in this extreme phenotypic response. Reciprocal gut microbiota transfers between B6 and 129 mice as well as antibiotic depletion causally linked gut microbes to Paclitaxel-induced pain sensitivity and resistance. Microglia proliferated in the spinal cords of Paclitaxel treated mice harboring the pain-sensitive B6 microbiota but not the pain-resistant 129 microbiota, which exhibited a notable absence of infiltrating immune cells. Paclitaxel decreased the abundance of Akkermansia muciniphila, which could compromise barrier integrity resulting in systemic exposure to bacterial metabolites and products – that acting via the gut-immune-brain axis – could result in altered brain function. Other bacterial taxa that consistently associated with both bacteria and pain as well as microglia and pain were identified, lending support to our hypothesis that microglia are causally involved in CIPN, and that gut bacteria are drivers of this phenotype.
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spelling pubmed-69372592020-01-06 Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain Ramakrishna, Chandran Corleto, Jose Ruegger, Paul M. Logan, Geoffrey D. Peacock, Beth B. Mendonca, Stacee Yamaki, Shanni Adamson, Trinka Ermel, Richard McKemy, David Borneman, James Cantin, Edouard M. Sci Rep Article Chemotherapy induced peripheral neuropathy (CIPN), a toxic side effect of some cancer treatments, negatively impacts patient outcomes and drastically reduces survivor’s quality of life (QOL). Uncovering the mechanisms driving chemotherapy-induced CIPN is urgently needed to facilitate the development of effective treatments, as currently there are none. Observing that C57BL/6 (B6) and 129SvEv (129) mice are respectively sensitive and resistant to Paclitaxel-induced pain, we investigated the involvement of the gut microbiota in this extreme phenotypic response. Reciprocal gut microbiota transfers between B6 and 129 mice as well as antibiotic depletion causally linked gut microbes to Paclitaxel-induced pain sensitivity and resistance. Microglia proliferated in the spinal cords of Paclitaxel treated mice harboring the pain-sensitive B6 microbiota but not the pain-resistant 129 microbiota, which exhibited a notable absence of infiltrating immune cells. Paclitaxel decreased the abundance of Akkermansia muciniphila, which could compromise barrier integrity resulting in systemic exposure to bacterial metabolites and products – that acting via the gut-immune-brain axis – could result in altered brain function. Other bacterial taxa that consistently associated with both bacteria and pain as well as microglia and pain were identified, lending support to our hypothesis that microglia are causally involved in CIPN, and that gut bacteria are drivers of this phenotype. Nature Publishing Group UK 2019-12-30 /pmc/articles/PMC6937259/ /pubmed/31889131 http://dx.doi.org/10.1038/s41598-019-56832-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ramakrishna, Chandran
Corleto, Jose
Ruegger, Paul M.
Logan, Geoffrey D.
Peacock, Beth B.
Mendonca, Stacee
Yamaki, Shanni
Adamson, Trinka
Ermel, Richard
McKemy, David
Borneman, James
Cantin, Edouard M.
Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain
title Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain
title_full Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain
title_fullStr Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain
title_full_unstemmed Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain
title_short Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain
title_sort dominant role of the gut microbiota in chemotherapy induced neuropathic pain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937259/
https://www.ncbi.nlm.nih.gov/pubmed/31889131
http://dx.doi.org/10.1038/s41598-019-56832-x
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