Electron-beam FLASH whole brain irradiation induced a unique changes of intestinal flora

Whole-brain radiotherapy (WBRT) is an important way to treat multiple metastases. Ultra-high dose rate (FLASH) can avoid neurotoxicity caused by conventional irradiation, it has attracted much attention. This study aims to study the difference of irradiation-induced intestinal flora between conventional dose rate and FLASH WBRT.

WBRT with 10 Gy was performed with electron-beam conventional irradiation (2 Gy/s) and electron-beam FLASH (eFLASH) irradiation (230 Gy/s). The intestinal feces and whole brain of mice were isolated after behavioral evaluation at 1st, 3rd and 10th weeks post-irradiation. HE staining and immunofluorescence were used to access the level of brain damage. The differences in intestinal microbes and transcription levels were detected by 16S rRNA gene sequencing and transcriptome sequencing, respectively.

eFLASH irradiation significantly reduced radiation neurotoxicity and had a long-term protective effect on cognitive function and learning and memory ability. Compared with conventional irradiation, eFLASH irradiation not only up-regulated the expression of genes related to neuronal regeneration and digestive system, but also induced more abundant intestinal microflora, especially the "probiotics" such as Lachnospiraceae and others, which were proved to play a role in radiation protection, increased significantly after eFLASH irradiation. The up-regulated microbiota after eFLASH irradiation was significantly positively correlated with genes related to neuronal development and regeneration, while significantly negatively correlated with genes related to inhibitory synapses. Additionally, conventional irradiation down-regulated microbial metabolism-related pathways, while FLASH did not.

In summary, we explored the unique gut microbiota changes induced by eFLASH WBRT for the first time, providing a theoretical basis for exploring the mechanism of action of FLASH.