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Changes in the gut microbiome community of nonhuman primates following radiation injury

BACKGROUND: Composition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive we...

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Autores principales: Kalkeri, Raj, Walters, Kevin, Van Der Pol, William, McFarland, Braden C., Fisher, Nathan, Koide, Fusataka, Morrow, Casey D., Singh, Vijay K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008626/
https://www.ncbi.nlm.nih.gov/pubmed/33781201
http://dx.doi.org/10.1186/s12866-021-02146-w
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author Kalkeri, Raj
Walters, Kevin
Van Der Pol, William
McFarland, Braden C.
Fisher, Nathan
Koide, Fusataka
Morrow, Casey D.
Singh, Vijay K.
author_facet Kalkeri, Raj
Walters, Kevin
Van Der Pol, William
McFarland, Braden C.
Fisher, Nathan
Koide, Fusataka
Morrow, Casey D.
Singh, Vijay K.
author_sort Kalkeri, Raj
collection PubMed
description BACKGROUND: Composition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive weapon, on the composition of the gut microbiome. Therefore, we sought to analyze alterations to the gut microbiome of nonhuman primates (NHPs) exposed to high doses of radiation. Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) 1 day prior and 1 and 4 days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD(70–80/60)). The 16S V4 rRNA sequences were extracted from each sample, followed by bioinformatics analysis using the QIIME platform. RESULTS: Alpha Diversity (Shannon Diversity Index), revealed no major difference between pre- and post-irradiation, whereas Beta diversity analysis showed significant differences in the microbiome after irradiation (day + 4) compared to baseline (pre-irradiation). The Firmicutes/Bacteriodetes ratio, a factor known to be associated with disruption of metabolic homeostasis, decreased from 1.2 to less than 1 post-radiation exposure. Actinobacillus, Bacteroides, Prevotella (Paraprevotellaceae family) and Veillonella genera were significantly increased by more than 2-fold and Acinetobacter and Aerococcus genus were decreased by more than 10-fold post-irradiation. Fifty-two percent (10/19) of animals exposed to radiation demonstrated diarrhea at day 4 post-irradiation. Comparison of microbiome composition of feces from animals with and without diarrhea at day 4 post-irradiation revealed an increase in Lactobacillus reuteri associated with diarrhea and a decrease of Lentisphaerae and Verrucomicrobioa phyla and Bacteroides in animals exhibiting diarrhea. Animals with diarrhea at day 4 post-irradiation, had significantly lower levels of Lentisphaere and Verrucomicrobia phyla and Bacteroides genus at baseline before irradiation, suggesting a potential association between the prevalence of microbiomes and differential susceptibility to radiation-induced diarrhea. CONCLUSIONS: Our findings demonstrate that substantial alterations in the microbiome composition of NHPs occur following radiation injury and provide insight into early changes with high-dose, whole-body radiation exposure. Future studies will help identify microbiome biomarkers of radiation exposure and develop effective therapeutic intervention to mitigate the radiation injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-021-02146-w.
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spelling pubmed-80086262021-03-31 Changes in the gut microbiome community of nonhuman primates following radiation injury Kalkeri, Raj Walters, Kevin Van Der Pol, William McFarland, Braden C. Fisher, Nathan Koide, Fusataka Morrow, Casey D. Singh, Vijay K. BMC Microbiol Research Article BACKGROUND: Composition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive weapon, on the composition of the gut microbiome. Therefore, we sought to analyze alterations to the gut microbiome of nonhuman primates (NHPs) exposed to high doses of radiation. Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) 1 day prior and 1 and 4 days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD(70–80/60)). The 16S V4 rRNA sequences were extracted from each sample, followed by bioinformatics analysis using the QIIME platform. RESULTS: Alpha Diversity (Shannon Diversity Index), revealed no major difference between pre- and post-irradiation, whereas Beta diversity analysis showed significant differences in the microbiome after irradiation (day + 4) compared to baseline (pre-irradiation). The Firmicutes/Bacteriodetes ratio, a factor known to be associated with disruption of metabolic homeostasis, decreased from 1.2 to less than 1 post-radiation exposure. Actinobacillus, Bacteroides, Prevotella (Paraprevotellaceae family) and Veillonella genera were significantly increased by more than 2-fold and Acinetobacter and Aerococcus genus were decreased by more than 10-fold post-irradiation. Fifty-two percent (10/19) of animals exposed to radiation demonstrated diarrhea at day 4 post-irradiation. Comparison of microbiome composition of feces from animals with and without diarrhea at day 4 post-irradiation revealed an increase in Lactobacillus reuteri associated with diarrhea and a decrease of Lentisphaerae and Verrucomicrobioa phyla and Bacteroides in animals exhibiting diarrhea. Animals with diarrhea at day 4 post-irradiation, had significantly lower levels of Lentisphaere and Verrucomicrobia phyla and Bacteroides genus at baseline before irradiation, suggesting a potential association between the prevalence of microbiomes and differential susceptibility to radiation-induced diarrhea. CONCLUSIONS: Our findings demonstrate that substantial alterations in the microbiome composition of NHPs occur following radiation injury and provide insight into early changes with high-dose, whole-body radiation exposure. Future studies will help identify microbiome biomarkers of radiation exposure and develop effective therapeutic intervention to mitigate the radiation injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-021-02146-w. BioMed Central 2021-03-29 /pmc/articles/PMC8008626/ /pubmed/33781201 http://dx.doi.org/10.1186/s12866-021-02146-w Text en © The Author(s) 2021 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Kalkeri, Raj
Walters, Kevin
Van Der Pol, William
McFarland, Braden C.
Fisher, Nathan
Koide, Fusataka
Morrow, Casey D.
Singh, Vijay K.
Changes in the gut microbiome community of nonhuman primates following radiation injury
title Changes in the gut microbiome community of nonhuman primates following radiation injury
title_full Changes in the gut microbiome community of nonhuman primates following radiation injury
title_fullStr Changes in the gut microbiome community of nonhuman primates following radiation injury
title_full_unstemmed Changes in the gut microbiome community of nonhuman primates following radiation injury
title_short Changes in the gut microbiome community of nonhuman primates following radiation injury
title_sort changes in the gut microbiome community of nonhuman primates following radiation injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008626/
https://www.ncbi.nlm.nih.gov/pubmed/33781201
http://dx.doi.org/10.1186/s12866-021-02146-w
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