Pelvic irradiation induces behavioural and neuronal damage through gut dysbiosis in a rat model

Chem Biol Interact. 2023 Dec 1:386:110775. doi: 10.1016/j.cbi.2023.110775. Epub 2023 Oct 20.

Abstract

Radiation exposure can cause gut dysbiosis and there is a positive correlation between gut microbial imbalance and radiation-induced side effects in cancer patients. However, the influence of radiation on the gut-brain axis (GBA) and its neurological consequences are not well understood. Therefore, this study aimed to investigate the impact of pelvic irradiation on gut microbiota and the brain. Sprague Dawley rats were irradiated with a single dose of 6 Gy, and faecal samples were collected at different time points (7 and 12-days post-irradiation) for microbial analysis. Behavioural, histological, and gene expression analysis were performed to assess the effect of microbial dysbiosis on the brain. The findings indicated alterations in microbial diversity, disrupted intestinal morphology and integrity, neuronal death-related brain changes, neuroinflammation and reduced locomotor activity. Hippocampal gene expression analysis also showed a reduced expression of neural plasticity-related genes. Overall, this study demonstrated that pelvic irradiation affects gut microbiota, intestinal morphology, integrity, brain neuronal maturation, neural plasticity gene expression, and behaviour.

Keywords: Gut dysbiosis; Gut microbiota; Gut-brain axis; Neural plasticity; Neurotoxicity; Pelvic radiotherapy.

MeSH terms

  • Animals
  • Brain
  • Dysbiosis*
  • Feces
  • Gastrointestinal Microbiome*
  • Humans
  • Rats
  • Rats, Sprague-Dawley