Specific Members of the Gut Microbiota are Reliable Biomarkers of Irradiation Intensity and Lethality in Large Animal Models of Human Health

Carbonero, Franck; Mayta, Alba; Bolea, Mathilde; Yu, Jiang-Zhou; Lindeblad, Matt; Lyubimov, Alex; Neri, Flavia; Szilàgyi, Erzsèbet; Smith, Brett; Halliday, Lisa; Bartholomew, Amelia

doi:10.1667/rr14975.1

Cited by 26 publications

(50 citation statements)

References 49 publications

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“…Interestingly signi cant increase in Bacteroidetes phylum at day + 4 post-irradiation observed in our study, differs from couple of previous studies [9,12]. These previous reports had shown either non-signi cant increase in Bacteroidetes in Chinese rhesus macaques after 3-days postirradiation with 6.8 Gy radiation [9] or no change in Bacteroidetes with 6.8/7.2/7.7 Gy radiation in Chinese rhesus macaques after 3days post-radiation [12].…”

Section: Discussioncontrasting

confidence: 99%

“…The observedchange in beta diversity was further strengthened with the signi cant decrease in the Firmicutes/Bacteriodes (F/B) ratio (from 1.2 at pre-radiation at day − 1 to 0.75 at post-irradiation day + 4), as Firmicutes/Bacteriodes (F/B) ratio is considered to be a signi cant indicator of gut microbiota composition [22,23]. Interestingly signi cant increase in Bacteroidetes phylum at day + 4 post-irradiation observed in our study, differs from couple of previous studies [9,12]. These previous reports had shown either non-signi cant increase in Bacteroidetes in Chinese rhesus macaques after 3-days postirradiation with 6.8 Gy radiation [9] or no change in Bacteroidetes with 6.8/7.2/7.7 Gy radiation in Chinese rhesus macaques after 3days post-radiation [12].…”

Section: Discussioncontrasting

confidence: 96%

“…In our study, though differences in alpha diversity were not observed, signi cant changes in beta diversity after irradiation consistent with the previous studies [9,12] were noticed. The observedchange in beta diversity was further strengthened with the signi cant decrease in the Firmicutes/Bacteriodes (F/B) ratio (from 1.2 at pre-radiation at day − 1 to 0.75 at post-irradiation day + 4), as Firmicutes/Bacteriodes (F/B) ratio is considered to be a signi cant indicator of gut microbiota composition [22,23].…”

Section: Discussionsupporting

confidence: 93%

“…Signi cant changes in speci c bacteria were observed in the current study. Changes in the levels of Actinobacteria, Veillonella and Bacteriodes genera post-irradiation observed in our study are similar to the previous reports [9,12]. However, in contrast to these previous reports [9,12], our study failed to observe signi cant changes in number of other genera (Spirochetes, Lactobacillus, Streptococcus, Treponema, Helicobacteria, Parabacteroides, Collinella and Prevotella).…”

Section: Discussionsupporting

confidence: 83%

“…In this study we sought to characterize the GI microbiome alterations following whole-body irradiation in NHPs (Chinese rhesus macaques). Similar to what has been attempted by others [9,12,13], we also sought to identify speci c microbial changes as a biomarker to predict adverse side effects (irradiation-induced diarrhea) following whole-body irradiation in these animals. We found that whole-body irradiation altered the diversity of the microbiome and relative representation of several key genera or species.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the Gut Microbiome Community of nonhuman primate following radiation injury

Kalkeri

Walters

Pol

et al. 2020

Preprint

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Abstract 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. Methods Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) one day prior and one and four days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD70 − 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. Conclusion 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.