Dysbiosis of Gut Microbiota Is Associated With the Progression of Radiation-Induced Intestinal Injury and Is Alleviated by Oral Compound Probiotics in Mouse Model.

Tian-Shu Zhao,Hao Zhou,Ming Li,Li-Wei Xie,Shang Cai,Lin-Feng Tang,Ye Tian,Shuguang Fang,Jia-Yu Xu,Chao Yang

doi:10.3389/fcimb.2021.717636

Abstract

The acute radiation-induced intestinal injury (RIII) has raised much concerns and is influenced by non-cytocidal radiation effects including the perturbations in gut microbiota. Although a number of studies have reported alteration in gut microbiota following radiation, little is known about its dynamic variation in the progression of acute RIII. In this study, mouse model were treated with total body irradiation (TBI) of 0, 4, 8 and 12 Gy, and the intestinal tissues and fecal samples were collected at 6 h, 3.5 d and 7 d post radiation. We found that the intestinal injuries were manifested in a radiation dose-dependent manner. Results from 16S rRNA gene sequencing demonstrated that the diversity of gut microbiota was not significantly affected at the prodromal stage of acute RIII, after 6 h of radiation. At the critical stage of acute RIII, after 3.5 d of radiation, the composition of gut microbiota was correlated with the radiation dose. The Pearson’s correlation analysis showed that the relative abundances of phylum Proteobacteria, genera Escherichia-Shigella and Eubacterium xylanophilum_group, and species Lactobacillus murinus exhibited linear correlations with radiation dose. At the recovery stage of acute RIII, after 7 d of radiation, the diversity of gut microbiota decreased as a whole, among which the relative abundance of phyla Proteobacteria and Bacteroides increased, while that of phylum Tenericutes and genus Roseburia decreased. The intra-gastric administration of compound probiotics for 14 days improved the survival duration of mice exposed to 9 Gy TBI, alleviated the intestinal epithelial injury and partially restored the diversity of gut microbiota. Our findings suggest that acute RIII is accompanied by the dysbiosis of gut microbiota, including its decreased diversity, reduced abundance of beneficial bacteria and increased abundance of pathogens. The gut microbiota cannot be used as sensitive biomarkers at the prodromal stage in acute RIII, but are potential biomarkers at the critical stage of acute RIII. The dysbiosis is persistent until the recovery stage of acute RIII, and interventions are needed to restore it. The administration of probiotics is an effective strategy to protect against acute RIII and subsequent dysbiosis.

Highlights

Due to the accidental exposure caused by the usage of radioactive or nuclear devices in nuclear power plants and terrorist attacks, the human beings may be exposed to high dose ionizing radiation (IR) in a short time, termed as acute radiation syndrome (ARS), and acute gastrointestinal syndrome is the main cause of early death in ARS (Kamiya et al, 2015)
A study by Nam et al found that the overall composition of gut microbiota was altered after pelvic radiotherapy; in particular, the phylum Firmicutes decreased by 10% and phylum Fusobacteria increased by 3% after radiotherapy (Nam et al, 2013)
This study suggested that the fecal bacteria could not be used as sensitive biomarkers at the prodromal stage of acute radiationinduced intestinal injury (RIII), but at the critical stage, phylum Proteobacteria, genera Escherichia-Shigella and Eubacterium xylanophilum_group, and species Lactobacillus murinus were identified as potential biomarkers

Summary

Introduction

Due to the accidental exposure caused by the usage of radioactive or nuclear devices in nuclear power plants and terrorist attacks, the human beings may be exposed to high dose ionizing radiation (IR) in a short time, termed as acute radiation syndrome (ARS), and acute gastrointestinal syndrome is the main cause of early death in ARS (Kamiya et al, 2015). Based on the development of 16S rRNA gene sequencing technology for decades, a number of studies have reported alteration in gut microbiota following radiation (Goudarzi et al, 2016; Cui et al, 2017; Reis Ferreira et al, 2019; Wang Z. et al, 2019), thereby influencing intestinal response to radiation (Gerassy-Vainberg et al, 2018; Kumagai et al, 2018; Wang Z. et al, 2019). Wang et al found that the pelvic radiotherapy caused a reduction in the alpha diversity of gut microbiota and an increase in the relative abundance ratio of Firmicutes to Bacteroidetes (Wang et al, 2015). Wang et al studied the alpha diversity of gut microbiota and found a decrease in the relative abundance of Bacteroides and an increase in that of Proteobacteria among patients with

Methods

Results

Conclusion