Influence of high fibre diets on the gut microbiota, prostate tumour growth and normal tissue toxicity following ionising radiation

<jats:p>Purpose: High dietary fibre intake has been linked to lower cancer risk, yet its role in prostate cancer treatment responses and radiotherapy tolerance remains unclear. We evaluated the effects of dietary fibres (inulin, pectin, beta glucan) on prostate tumour growth, gut microbiota and intestinal response to ionising radiation (IR) in murine models. Methods: Male FVB and C57BL/6J mice were injected with murine Myc CaP (FVB), RM 1 or DVL3 (C57BL/6J) prostate tumour cells and fed a low fibre (0.2% cellulose) or high fibre diet (10% inulin, pectin or beta glucan). Some mice had tumour irradiation (6 Gy). Tumour volume, caecal weight and faecal microbiota relative abundance (by 16S rRNA gene sequencing) were analysed. Caecal contents fermentation acids were quantified by gas chromatography. The effects of dietary fibre on intestinal acute normal tissue toxicity post irradiation (10 to 14 Gy) were assessed by intestinal crypt assay. Results: Inulin delayed average tumour growth in all models. Inulin and beta glucan prolonged post IR tumour control versus 0.2% cellulose (all p &lt;0.05), in some but not all mice. Inulin, pectin and beta glucan increased faecal acetate concentrations post IR and mice demonstrated responder (R) vs non responder (NR) phenotypes to diet/IR, associated with Bifidobacterium (inulin R), Lactobacillus and Parasutterella (pectin R) and Muribaculacaeae and Muribaculum (beta glucan R). High fibre fed mice had enhanced intestinal crypt regeneration following 12 Gy compared to 0.2% cellulose fed mice. Conclusions: High fibre diets slowed prostate tumour growth both alone and following 6 Gy IR, while protecting small intestines from radiation induced injury. Effects may have been mediated via increased microbiota driven metabolite production and enhanced epithelial regeneration, but more mechanistic work is required to explore causality. The differences in individual responses to various fibres should be investigated further, as this may have relevance to adopting dietary fibre supplementation strategies in human radiotherapy patients, and may reflect the recognised importance of an individuals baseline microbiota on dietary effects.</jats:p>