Irradiation-Induced Intestinal Damage Is Recovered by the Indigenous Gut BacteriaLactobacillus acidophilus

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 ofLactobacilluswas reduced at early time point post-irradiation; however, it was recovered at late time point. Oligotyping analysis within theLactobacillusgenus indicated thatLactobacillus-related oligotype 1 (OT1) includingLactobacillus acidophilusmight drive recovery after irradiation as it was associated with increased long-term numbers post-exposure. We showed that treatment with heat-killedL. acidophilusrescued 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 bacteriaL. acidophilusenhance intestinal epithelial function with respect to irradiation-induced intestinal damage by improving intestinal stem cell function and cell differentiation.