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Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure

BACKGROUND: The mammalian gut harbors very complex and diverse microbiota that play an important role in intestinal homeostasis and host health. Exposure to radiation results in dysbiosis of the gut microbiota leading to detrimental pathophysiological changes to the host. To alleviate the effects of...

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Autores principales: Cheema, Amrita K., Li, Yaoxiang, Singh, Jatinder, Johnson, Ryan, Girgis, Michael, Wise, Stephen Y., Fatanmi, Oluseyi O., Kaytor, Michael 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/PMC8501697/
https://www.ncbi.nlm.nih.gov/pubmed/34627406
http://dx.doi.org/10.1186/s42523-021-00132-1
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author Cheema, Amrita K.
Li, Yaoxiang
Singh, Jatinder
Johnson, Ryan
Girgis, Michael
Wise, Stephen Y.
Fatanmi, Oluseyi O.
Kaytor, Michael D.
Singh, Vijay K.
author_facet Cheema, Amrita K.
Li, Yaoxiang
Singh, Jatinder
Johnson, Ryan
Girgis, Michael
Wise, Stephen Y.
Fatanmi, Oluseyi O.
Kaytor, Michael D.
Singh, Vijay K.
author_sort Cheema, Amrita K.
collection PubMed
description BACKGROUND: The mammalian gut harbors very complex and diverse microbiota that play an important role in intestinal homeostasis and host health. Exposure to radiation results in dysbiosis of the gut microbiota leading to detrimental pathophysiological changes to the host. To alleviate the effects of irradiation, several candidate countermeasures are under investigation. BIO 300, containing synthetic genistein formulated as an amorphous solid dispersion or as an aqueous suspension of nanoparticles, is a promising candidate under advanced development. The aim of this study was to investigate the effects of BIO 300 on the gut microbiome and metabolome of mice exposed to (60)Co gamma-radiation. The gut microbiota and metabolome of control and drug-treated mice exposed to radiation was characterized by bacterial 16S rRNA amplicon sequencing and untargeted metabolomics. RESULTS: We found that irradiation altered the Firmicutes/Bacteroidetes ratio and significantly decreased the relative abundance of Lactobacillus, both in BIO 300-treated and control mice; however, the ratio returned to near normal levels in BIO 300-treated mice by day 14 post-irradiation. Concomitantly, we also observed corrective shifts in metabolic pathways that were perturbed after irradiation. CONCLUSIONS: Overall, the data presented show that radiation exposure led to a relative depletion of commensals like Lactobacillus leading to an inflammatory metabolic phenotype while the majority of the drug-treated mice showed alleviation of this condition primarily by restoration of normal gut microbiota. These results indicate that the radioprotective effects of BIO 300, at least in part, may involve correction of the host-microbiome metabolic axis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-021-00132-1.
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spelling pubmed-85016972021-10-20 Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure Cheema, Amrita K. Li, Yaoxiang Singh, Jatinder Johnson, Ryan Girgis, Michael Wise, Stephen Y. Fatanmi, Oluseyi O. Kaytor, Michael D. Singh, Vijay K. Anim Microbiome Research Article BACKGROUND: The mammalian gut harbors very complex and diverse microbiota that play an important role in intestinal homeostasis and host health. Exposure to radiation results in dysbiosis of the gut microbiota leading to detrimental pathophysiological changes to the host. To alleviate the effects of irradiation, several candidate countermeasures are under investigation. BIO 300, containing synthetic genistein formulated as an amorphous solid dispersion or as an aqueous suspension of nanoparticles, is a promising candidate under advanced development. The aim of this study was to investigate the effects of BIO 300 on the gut microbiome and metabolome of mice exposed to (60)Co gamma-radiation. The gut microbiota and metabolome of control and drug-treated mice exposed to radiation was characterized by bacterial 16S rRNA amplicon sequencing and untargeted metabolomics. RESULTS: We found that irradiation altered the Firmicutes/Bacteroidetes ratio and significantly decreased the relative abundance of Lactobacillus, both in BIO 300-treated and control mice; however, the ratio returned to near normal levels in BIO 300-treated mice by day 14 post-irradiation. Concomitantly, we also observed corrective shifts in metabolic pathways that were perturbed after irradiation. CONCLUSIONS: Overall, the data presented show that radiation exposure led to a relative depletion of commensals like Lactobacillus leading to an inflammatory metabolic phenotype while the majority of the drug-treated mice showed alleviation of this condition primarily by restoration of normal gut microbiota. These results indicate that the radioprotective effects of BIO 300, at least in part, may involve correction of the host-microbiome metabolic axis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-021-00132-1. BioMed Central 2021-10-09 /pmc/articles/PMC8501697/ /pubmed/34627406 http://dx.doi.org/10.1186/s42523-021-00132-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Cheema, Amrita K.
Li, Yaoxiang
Singh, Jatinder
Johnson, Ryan
Girgis, Michael
Wise, Stephen Y.
Fatanmi, Oluseyi O.
Kaytor, Michael D.
Singh, Vijay K.
Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure
title Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure
title_full Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure
title_fullStr Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure
title_full_unstemmed Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure
title_short Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure
title_sort microbiome study in irradiated mice treated with bio 300, a promising radiation countermeasure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501697/
https://www.ncbi.nlm.nih.gov/pubmed/34627406
http://dx.doi.org/10.1186/s42523-021-00132-1
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