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

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Abstract 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, β-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 β-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 (10–14 Gy) were assessed by intestinal crypt assay. Results Inulin delayed average tumour growth in all models. Inulin and β-glucan prolonged post-IR tumour control versus 0.2% cellulose (all p <0.05), in some but not all mice. Inulin, pectin and β-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 (β-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 individual’s baseline microbiota on dietary effects.

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