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

Amrita K Cheema,Jatinder Singh,Stephen Y Wise,Michael Girgis,Ryan Johnson,Yaoxiang Li,Oluseyi O Fatanmi,Vijay K Singh,Michael D Kaytor

doi:10.1186/s42523-021-00132-1

Abstract

BackgroundThe 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 60Co 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.ResultsWe 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.ConclusionsOverall, 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.

Highlights

The mammalian gut harbors very complex and diverse microbiota that play an important role in intestinal homeostasis and host health
Treatment with BIO 300 Oral Suspension or Oral Powder significantly increases survival To investigate the radioprotective efficacy of BIO 300 Oral suspension (OS) and BIO 300 Oral powder (OP), mice were administered a dose of 200 mg/kg po twice daily for six consecutive days prior to irradiation
Mice were exposed to 9.2 Gy (LD70/30) 60Co γ-radiation and survival was monitored for 30 days

Summary

Introduction

The mammalian gut harbors very complex and diverse microbiota that play an important role in intestinal homeostasis and host health. At lower doses (2–6 Gy), irradiation damages the hematopoietic system resulting in neutropenia and thrombocytopenia, Gut microbiota plays a crucial role in intestinal homeostasis and provide several metabolic and immunoregulatory functions such as the production of vitamins, amino acids, short chain fatty acids and other metabolites, the biotransformation of bile, and the coevolution of the Cheema et al anim microbiome (2021) 3:71 host’s immature immune system [5]. Short chain fatty acids are important for gut homeostasis and health This is due to their role as an energy source for gut epithelial cells, thereby improving the integrity of the host mucosal barrier and offering immunomodulation and protection against pathogens in the gut [6]. Stasis of gut microbiota is important and its dysbiosis has been implicated in diseases such as inflammatory bowel disease, metabolic disease, obesity, and cancer [10]

Objectives

Methods

Results

Conclusion