Irradiation-Induced Intestinal Damage Is Recovered by the Indigenous Gut Bacteria Lactobacillus acidophilus.

Yun Kyung Lee,Hyun Jung Ji,Panida Sittipo,Gi-Ung Kang,Huy Quang Pham,Ho Seong Seo,Chang Eon Park,Yong Zhi,Jae-Ho Shin,Ayeung Jang

doi:10.3389/fcimb.2020.00415

Abstract

The intestinal tract is one of the most sensitive organs following irradiation. The protective effect of specific indigenous microbiota on irradiation-induced damage to intestinal epithelial cells has not been reported. Mice were irradiated with a single dose of 6 Gy of gamma rays. The intestinal damage was analyzed by histopathology. Intestinal stemness and differentiation were determined by intestinal organoid culture. Microbiota community was observed by high-throughput 16S rRNA gene sequencing and oligotyping analysis. We showed that distal small intestine was damaged by sublethal dose of gamma irradiation. Intestinal organoids derived from the irradiated mice showed defects in budding and mucin expression, suggesting the detrimental effect of irradiation on the intestinal stemness and differentiation. In addition, irradiation reduced intestinal immunoglobulin A level, concomitant with decreased microbiota diversity based on our high-throughput 16S rRNA gene sequencing data. Especially, the relative abundance of Lactobacillus was reduced at early time point post-irradiation; however, it was recovered at late time point. Oligotyping analysis within the Lactobacillus genus indicated that Lactobacillus-related oligotype 1 (OT1) including Lactobacillus acidophilus might drive recovery after irradiation as it was associated with increased long-term numbers post-exposure. We showed that treatment with heat-killed L. acidophilus rescued the budding-impaired organoids and induced sufficient differentiation in epithelial cells, and particularly mucin-producing cells, in intestinal organoids. This study provides the first evidence that the indigenous gut bacteria L. acidophilus enhance intestinal epithelial function with respect to irradiation-induced intestinal damage by improving intestinal stem cell function and cell differentiation.

Highlights

Gamma radiation is widely used for clinical applications (Deacon et al, 2008; De Andrade et al, 2014)
Our result suggested that the distal small intestine was the most radiosensitive part of the intestinal tract
From 77,444 sequences of this genus, based on 80 different operational taxonomic unit (OTU) identifiers corresponding to specific sequences, we found three dominant oligotypes (OT1, OT2, and OT3) with different assigned species information based on BLASTn analysis results on 16S ribosomal RNA sequences (Bacteria and Archaea) database (Table S2)

Summary

Introduction

Gamma radiation is widely used for clinical applications (Deacon et al, 2008; De Andrade et al, 2014). Sublethal doses (6– 10 Gy) of gamma irradiation have been used effectively for bone marrow transplantation, immunosuppression, and cancer therapy. The gastrointestinal tract is one of the most radio-sensitive organs following exposure to sublethal doses of gamma irradiation (Hauer-Jensen et al, 2007; Donnelly et al, 2010; Ki et al, 2014). IECs, can recognize and respond to signals generated by the intestinal microbiota or associated molecules, resulting in a reinforced intestinal barrier function and the maintenance of intestinal homeostasis (Round and Mazmanian, 2009; Peterson and Artis, 2014; Nigro and Sansonetti, 2015; Pan et al, 2018). IECs form the barrier and function differently based on specific cell types. IECs are classified into different specific functional cell types including intestinal stem cells (ISCs), Paneth cells (lysozyme-producing cells), which are located in the intestinal crypts, goblet cells (mucus-secreting cells), enteroendocrine cells, and enterocytes (absorptive cells), which are localized in the intestinal villi (Fair et al, 2018)

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Conclusion