scholarly journals Changes in the Gut Microbiome Community of Nonhuman Primate Following Radiation Injury

2020 ◽  
Author(s):  
Raj Kalkeri ◽  
Kevin Walters ◽  
William Van Der Pol ◽  
Braden C. McFarland ◽  
Nathan Fisher ◽  
...  

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. 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. 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.

2020 ◽  
Author(s):  
Raj Kalkeri ◽  
Kevin Walters ◽  
William Van Der Pol ◽  
Braden C. McFarland ◽  
Nathan Fisher ◽  
...  

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.


2020 ◽  
Author(s):  
Raj Kalkeri ◽  
Kevin Walters ◽  
William Van Der Pol ◽  
Braden C. McFarland ◽  
Nathan Fisher ◽  
...  

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. 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. 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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Raj Kalkeri ◽  
Kevin Walters ◽  
William Van Der Pol ◽  
Braden C. McFarland ◽  
Nathan Fisher ◽  
...  

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. 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 (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. 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.


2017 ◽  
Vol 2 (3) ◽  
pp. 310
Author(s):  
Poonam Rana ◽  
Ahmad Raza Khan ◽  
Mamta Aryabhushan Gupta ◽  
Subash Khushu

Whole body radiation exposure induced injury may occur during medical or industrial accidents as well as during terrorist radiation exposure scenario. A lot of information is available on alterations in brain function and metabolism post localised cranial irradiation; changes in brain associated with whole body radiation exposure are still limited. The present study has been conducted to assess early differential effect of low and high whole body radiation exposure on hippocampus neurometabolites using <em>in vivo</em> proton magnetic resonance spectroscopy (1H MRS). Hippocampal 1H MRS was carried out in controls (n = 6) and irradiated mice exposed to 3 Gy, 5 Gy, and 8 Gy of radiation (n = 6 in each group) at different time points i.e., day 0, 1, 3, 5 and 10 post irradiation at 7 T MRI system. Quantitative assessment of the neurometabolites was done using LCModel. The results revealed significant decrease in myoionisitol (mI)/creatine (tCr) and taurine (tau)/tCr in animals exposed to 5 Gy and 8 Gy dose compared to controls. In 3 Gy dose group, none of the metabolites showed significant alterations at any of the time point post irradiation as compared to controls. Overall our findings suggest differential change in hippocampal volume regulatory mechanism associated neuro-metabolites following whole body radiation exposure with maximum reduction in case of high dose group. We speculate that these alterations may be a consequence of oxidative stress, neuro inflammation or systemic inflammatory response following whole body radiation exposure.


2019 ◽  
Author(s):  
Sebastian Heinzel ◽  
Velma T. E. Aho ◽  
Ulrike Suenkel ◽  
Anna-Katharina von Thaler ◽  
Claudia Schulte ◽  
...  

AbstractObjectivesAlterations of the gut microbiome in Parkinson’s disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition.MethodsEstablished risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants.ResultsAmong risk and prodromal markers, physical inactivity, constipation and age showed associations with α- and β-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with β-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes-enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations.InterpretationSeveral risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.


2017 ◽  
Vol 1 (4) ◽  
pp. 325-332 ◽  
Author(s):  
Abigail R. Basson ◽  
Anisha Wijeyesekera

There is growing interest in the role of the gut microbiome in human health and disease. This unique complex ecosystem has been implicated in many health conditions, including intestinal disorders, inflammatory skin diseases and metabolic syndrome. However, there is still much to learn regarding its capacity to affect host health. Many gut microbiome research studies focus on compositional analysis to better understand the causal relationships between microbial communities and disease phenotypes. Yet, microbial diversity and complexity is such that community structure alone does not provide full understanding of microbial function. Metabolic phenotyping is an exciting field in systems biology that provides information on metabolic outputs taking place in the system at a given moment in time. These readouts provide information relating to by-products of endogenous metabolic pathways, exogenous signals arising from diet, drugs and other lifestyle and environmental stimuli, as well as products of microbe–host co-metabolism. Thus, better understanding of the gut microbiome and host metabolic interplay can be gleaned using such analytical approaches. In this review, we describe research findings focussed on gut microbiota–host interactions, for functional insights into the impact of microbiome composition on host health. We evaluate different analytical approaches for capturing metabolic activity and discuss analytical methodological advancements that have made a contribution to the field. This information will aid in developing novel approaches to improve host health in the future, and therapeutic modulation of the microbiome may soon augment conventional clinical strategies.


2009 ◽  
Vol 297 (3) ◽  
pp. E767-E773 ◽  
Author(s):  
Susan A. Phillips ◽  
Jacqueline Kung ◽  
Theodore P. Ciaraldi ◽  
Charles Choe ◽  
Louis Christiansen ◽  
...  

Adiponectin, an insulin-sensitizing factor secreted from adipose tissue, is decreased in individuals with type 2 diabetes (T2D) and increased in response to thiazolidinedione (TZD) therapy. Changes in its secretion and assembly into higher-order forms affect insulin sensitivity. To determine the relative potency of TZDs on intra-adipocyte multimerization and secretion of adiponectin, we assessed the impact of in vivo low- or high-dose rosiglitazone treatment alone or combined with metformin in subjects with T2D. T2D subjects received high-dose rosiglitazone (8 mg/day), high-dose metformin (2,000 mg/day), or low-dose combination rosiglitazone-metformin therapy (4 mg + 1,000 mg/day) for 4 mo. All subjects were then switched to high-dose rosiglitazone-metformin combination therapy (8 mg + 2,000 mg/day) for another 4 mo. Low-dose rosiglitazone increased serum adiponectin, whereas the high dose increased both adipocyte content and serum adiponectin levels. TZDs selectively increased the percentage of circulating adiponectin in the potent, high-molecular-weight (HMW) form. No TZD effects were evident on multimer distribution in the cell. Expression of the chaperone protein ERp44, which retains adiponectin within the cell, was decreased by TZD treatment. No changes occurred in Ero1-Lα expression. Metformin had no effect on any of these measures. Increases in adiponectin correlated with improvements in insulin sensitivity. In vivo, TZDs have apparent dose-dependent effects on cellular and secreted adiponectin. TZD-mediated improvements in whole body insulin sensitivity are associated with increases in circulating but not cellular levels of the HMW adiponectin multimer. Finally, TZDs promote the selective secretion of HMW adiponectin, potentially, in part, through decreasing the expression of the adiponectin-retaining protein ERp44.


2020 ◽  
Author(s):  
Thibault Scalvenzi ◽  
Isabelle Clavereau ◽  
Mickaël Bourge ◽  
Nicolas Pollet

AbstractBackgroundThe microorganism world living in amphibians is still largely under-represented and under-studied in the literature. Among anuran amphibians, African clawed frogs of the Xenopus genus stand as well-characterized models with an in-depth knowledge of their developmental biological processes including their metamorphosis. We used different approaches including flow cytometry and 16s rDNA gene metabarcoding to analyze the succession of microbial communities and their activities across different body habitats of Xenopus tropicalis. We used metagenomic and metatranscriptomic sequencing to evaluate the metabolic capacity of the premetamorphic tadpole’s gut microbiome.ResultsWe analyzed the bacterial components of the Xenopus gut microbiota, the adult gut biogeography, the succession of communities during ontogeny, the impact of the alimentation in shaping the tadpole’s gut bacterial communities, the transmission of skin and fecal bacteria to the eggs. We also identified the most active gut bacteria and their metabolic contribution to tadpole physiology including carbohydrate breakdown, nitrogen recycling, essential amino-acids and vitamin biosynthesis.ConclusionsWe present a comprehensive new microbiome dataset of a laboratory amphibian model. Our data provide evidences that studies on the Xenopus tadpole model can shed light on the interactions between a vertebrate host and its microbiome. We interpret our findings in light of bile acids being key molecular components regulating the gut microbiome composition during amphibian development and metamorphosis. Further studies into the metabolic interactions between amphibian tadpoles and their microbiota during early development and metamorphosis should provide useful information on the evolution of host-microbiota interactions in vertebrates.


2018 ◽  
Author(s):  
Tam T.T. Tran ◽  
Simone Corsini ◽  
Lee Kellingray ◽  
Claire Hegarty ◽  
Gwénaëlle Le Gall ◽  
...  

AbstractApolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer’s disease. Numerous studies have provided insights into the pathological mechanisms. However, a comprehensive understanding of the impact ofAPOEgenotype on microflora speciation and metabolism is completely lacking. The aim of this study was to investigate the association betweenAPOEgenotype and the gut microbiome composition in human andAPOE-targeted replacement (TR,APOE3andAPOE4) transgenic mice. Faecal microbiota amplicon sequencing from matched individuals with differentAPOEgenotypes revealed no significant differences in overall microbiota diversity (alpha or beta diversity) in group-aggregated humanAPOEgenotypes. However, several bacterial taxa showed significantly different relative abundance betweenAPOEgenotypes. Notably, we detected an association ofPrevotellaceaeandRuminococcaceaeand several butyrate-producing genera abundances withAPOEgenotypes. These findings were confirmed by comparing the gut microbiota ofAPOE-TR mice. Furthermore, metabolomic analysis of faecal water from murine samples detected significant differences in microbe-associated amino acids and short-chain fatty acids betweenAPOEgenotypes. Together, the findings indicate thatAPOEgenotype associated with specific gut microbiome profiles in both humans and inAPOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential therapeutic target to mitigate the deleterious impact of theAPOE4allele on cognitive decline and the prevention and treatment of AD.


Author(s):  
Davoud Kianifard ◽  
Seyyed Maysam Mousavi Shoar ◽  
Morteza Fallah Karkan ◽  
Ahmed Aly

Background: Quinine (QU) as an anti-malarial drug induces alterations in testicular tissue. Toxic effects of monosodium glutamate (MSG) on the male reproductive system have been recognized. Objective: To investigate the impact of MSG administration on the intensity of gonadotoxicity of QU. Materials and Methods: Sixty eight-wk old Wistar rats weighing 180-200 gr were divided into six groups (n = 10/each): the first group as a control; the second and third groups received low and high doses of MSG (2 & 4 gr/kg i.p.), respectively, for 28 days; the fourth group received QU for seven days (25 mg/kg); and in the fifth and sixth groups, QU was gavaged following the MSG administration (MSG + QU) from day 22 to day 28. Serum testosterone and malondialdehyde (MDA) levels were measured. Testes samples were prepared for tissue MDA levels, histomorphometry, and immunohistochemistry of p53. Sperm analysis was performed on cauda epididymis. Results: Serum and tissue MDA levels were increased in treated groups compared to the control group. This increment was higher in the MSG + QU groups. The testosterone levels were reduced significantly (p < 0.0001) in all treated groups. In addition, histomorphometric indices and tubular epithelium population were reduced significantly (p < 0.0001) in QU, MSG + QU, and consequently in high-dose MSG, QU, MSG + QU groups. All spermatogenic indices were reduced in the treated groups, particularly in the MSG + QU groups. Sperm motility and viability indices were reduced significantly (p = 0.003) in the MSG + QU groups. Finally, the overexpression of p53 was observed in the MSG + QU groups. Conclusion: The administration of MSG before and during QU therapy may intensify testicular tissue alterations. Key words: Male reproductive system, Monosodium glutamate, Quinine hydrochloride, Rat.


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