Background:
The neurological complications of cancer therapy remain a significant supportive care challenge with limited understanding of pathobiology, however, recent studies have suggested that the microbiota-gut-brain axis may play a role. This study therefore aimed to investigate the effect of a high fibre diet in a model of chemotherapy-induced neuroinflammation. We hypothesised that the high fibre diet would support gut microbial resistance and mitigate neuroinflammation.
Methods:
Female C57Bl/6 mice (N=24) were treated with 5-fluorouracil (400 mg/per kg) or vehicle control with or without a high fibre diet (high amylose starch) intervention. The high fibre diet was given for 1 week prior to 5-FU and until completion of the study. All mice were terminated 16 days after 5-FU. Immunofluorescence staining for glial acidic fibrillary protein (GFAP) was performed on brain tissue to evaluate astrocyte abundance (previously identified as a hallmark of 5-FU-induced neuroinflammation). RT-PCR was also performed for Il-1β on brain homogenates. Faecal samples were collected longitudinally for microbiota analysis using 16S. Short chain fatty acids (SCFAs) were also quantified using GC-MS.
Results:
A profound decrease in GFAP expression was observed in the CA1 region (p<0.0001) and dentate gyrus (p=0.0359) of the hippocampus as well as the midbrain (p=0.0215), in 5-FU treated animals receiving high fibre diet when compared to 5-FU treated controls. A significant decrease in IL-1β expression was also observed between in animals on the high-fibre diet compared to controls following 5-FU (p=0.0410). Propionic acid concentrations of caecal contents were increased in animals treated with the high fibre diet and shared a negative correlation with GFAP expression in CA1 of the hippocampus (p=0.0252).
Discussion:
These data strongly suggest that fibre supplementation reduces neuroinflammation via the production of propionic acid, warranting further investigation into how these findings can be translated to improve neurological outcomes for people with cancer.