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Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity
Methotrexate (MTX) is a typical chemotherapeutic drug that is widely used in the treatment of various malignant diseases as well as autoimmune diseases, with gastrointestinal toxicity being its most prominent complication which could have a significant effect on the prognosis of patients. Yet effect...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524152/ https://www.ncbi.nlm.nih.gov/pubmed/31983316 http://dx.doi.org/10.1080/19490976.2020.1714401 |
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author | Tang, Duozhuang Zeng, Ting Wang, Yiting Cui, Hui Wu, Jianying Zou, Bing Tao, Zhendong Zhang, Liu Garside, George B. Tao, Si |
author_facet | Tang, Duozhuang Zeng, Ting Wang, Yiting Cui, Hui Wu, Jianying Zou, Bing Tao, Zhendong Zhang, Liu Garside, George B. Tao, Si |
author_sort | Tang, Duozhuang |
collection | PubMed |
description | Methotrexate (MTX) is a typical chemotherapeutic drug that is widely used in the treatment of various malignant diseases as well as autoimmune diseases, with gastrointestinal toxicity being its most prominent complication which could have a significant effect on the prognosis of patients. Yet effective ways to alleviate such complications remains to be explored. Here we show that 30% dietary restriction (DR) for 2 weeks dramatically increased the survival rate of 2-month-old female mice after lethal-dose MTX exposure. DR significantly reduced intestinal inflammation, preserved the number of basal crypt PCNA-positive cells, and protected the function of intestinal stem cells (ISCs) after MTX treatment. Furthermore, ablating intestinal microbiota by broad-spectrum antibiotics completely eliminated the protective effect achieved by DR. 16S rRNA gene deep-sequencing analysis revealed that short-term DR significantly increased the Lactobacillus genus, with Lactobacillus rhamnosus GG gavage partially mimicking the rescue effect of DR on the intestines of ad libitum fed mice exposed to lethal-dose MTX. Together, the current study reveals that DR could be a highly effective way to alleviate the lethal injury in the intestine after high-dose MTX treatment, which is functionally mediated by increasing the protective intestinal microbiota taxa in mice. Keywords: Dietary restriction, Methotrexate, Gut microbiota, Intestinal stem cells, intestinal toxicity |
format | Online Article Text |
id | pubmed-7524152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-75241522020-10-06 Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity Tang, Duozhuang Zeng, Ting Wang, Yiting Cui, Hui Wu, Jianying Zou, Bing Tao, Zhendong Zhang, Liu Garside, George B. Tao, Si Gut Microbes Research Paper/Report Methotrexate (MTX) is a typical chemotherapeutic drug that is widely used in the treatment of various malignant diseases as well as autoimmune diseases, with gastrointestinal toxicity being its most prominent complication which could have a significant effect on the prognosis of patients. Yet effective ways to alleviate such complications remains to be explored. Here we show that 30% dietary restriction (DR) for 2 weeks dramatically increased the survival rate of 2-month-old female mice after lethal-dose MTX exposure. DR significantly reduced intestinal inflammation, preserved the number of basal crypt PCNA-positive cells, and protected the function of intestinal stem cells (ISCs) after MTX treatment. Furthermore, ablating intestinal microbiota by broad-spectrum antibiotics completely eliminated the protective effect achieved by DR. 16S rRNA gene deep-sequencing analysis revealed that short-term DR significantly increased the Lactobacillus genus, with Lactobacillus rhamnosus GG gavage partially mimicking the rescue effect of DR on the intestines of ad libitum fed mice exposed to lethal-dose MTX. Together, the current study reveals that DR could be a highly effective way to alleviate the lethal injury in the intestine after high-dose MTX treatment, which is functionally mediated by increasing the protective intestinal microbiota taxa in mice. Keywords: Dietary restriction, Methotrexate, Gut microbiota, Intestinal stem cells, intestinal toxicity Taylor & Francis 2020-01-26 /pmc/articles/PMC7524152/ /pubmed/31983316 http://dx.doi.org/10.1080/19490976.2020.1714401 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Research Paper/Report Tang, Duozhuang Zeng, Ting Wang, Yiting Cui, Hui Wu, Jianying Zou, Bing Tao, Zhendong Zhang, Liu Garside, George B. Tao, Si Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity |
title | Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity |
title_full | Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity |
title_fullStr | Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity |
title_full_unstemmed | Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity |
title_short | Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity |
title_sort | dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity |
topic | Research Paper/Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524152/ https://www.ncbi.nlm.nih.gov/pubmed/31983316 http://dx.doi.org/10.1080/19490976.2020.1714401 |
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