This preclinical study investigated whether dietary high fibre supplementation modifies the gut microbiota, alters prostate tumour growth, and changes normal tissue tolerance to ionising radiation (IR) in mouse models. The authors compared a low fibre control diet (0.2% cellulose) with three high fibre diets containing 10% inulin, pectin, or beta glucan. Outcomes included tumour growth with and without focal tumour irradiation, faecal and caecal measures of fermentation, faecal microbiota by 16S rRNA gene sequencing, and intestinal crypt regeneration after high-dose IR.
Male mice of two strains were used: FVB mice injected with Myc CaP tumour cells, and C57BL/6J mice injected with RM1 or DVL3 prostate tumour cells. Diet assignment was either low fibre (0.2% cellulose) or one of three high fibre diets (10% inulin, 10% pectin, or 10% beta glucan). Tumour-bearing mice in some groups received a single 6 Gy dose of tumour-directed ionising radiation. Intestinal acute normal tissue toxicity was assessed separately using an intestinal crypt assay after exposures in the 10–14 Gy range, and specifically crypt regeneration was assessed after 12 Gy.
The control diet contained 0.2% cellulose. High fibre interventions consisted of 10% of a single fibre type: inulin, pectin, or beta glucan. Tumour irradiation used a 6 Gy single dose for assessment of tumour control. Higher doses (10–14 Gy) were applied to evaluate acute intestinal injury and regenerative capacity using the crypt assay. Caecal contents were analysed for fermentation acids by gas chromatography and faecal microbiota composition by 16S rRNA sequencing.
High fibre feeding produced measurable effects on tumour kinetics. Inulin feeding delayed average prostate tumour growth across the models tested. After a 6 Gy tumour-directed dose, both inulin and beta glucan groups showed prolonged tumour control compared with the 0.2% cellulose control in some, but not all, mice. The study reports heterogeneity in responses among individuals, indicating that not all animals benefited equivalently from a given fibre.
High fibre diets altered microbial fermentation and metabolite output. Inulin, pectin and beta glucan increased faecal acetate concentrations post irradiation relative to the low fibre control, consistent with enhanced microbial fermentation of dietary substrates. Faecal microbiota composition changes were analysed by 16S rRNA gene sequencing; associations between taxa and response phenotypes were identified.
Animals segregated into responder (R) and non-responder (NR) phenotypes to diet plus IR. Specific taxa were associated with responder status for different fibres: Bifidobacterium was linked with inulin responders, Lactobacillus and Parasutterella with pectin responders, and Muribaculaceae / Muribaculum with beta glucan responders. These associations suggest that baseline or diet-modified microbiota composition may influence the antitumour and tissue-protective effects of individual fibres.
High fibre-fed mice exhibited enhanced intestinal crypt regeneration following exposure to 12 Gy compared with mice on 0.2% cellulose. This finding indicates reduced acute small intestinal injury and improved epithelial regenerative capacity in high fibre conditions. The authors propose that microbiota-driven metabolite production and enhanced epithelial regeneration may underlie the protective effects, although mechanistic causality was not established in this study.
In these murine models, high fibre diets slowed prostate tumour growth both alone and after a 6 Gy tumour-directed dose in some animals, and they protected small intestinal epithelium from radiation-induced injury as assessed by crypt regeneration. The study links specific microbial taxa and increased acetate production to responder phenotypes, but the authors acknowledge that further mechanistic work is required to establish causal relationships. The observed heterogeneity in individual responses highlights the potential importance of baseline microbiota when considering dietary fibre supplementation strategies alongside radiotherapy in humans. As this report is a preprint, findings have not been peer reviewed. Details on mechanisms, longitudinal clinical relevance, and human translational data were not reported in the source and require additional study.