Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity
Chee Kin Then, Salomé Paillas, Aliu Moomin, Mariya Misheva, Rachel Moir, Susan M. Hay, David Bremner, K. Roberts, Ellen E. Smith, Zeynab Heidari, Daniel Sescu, Xuedan Wang, Alejandro Suárez‐Bonnet, Nadine Hay, Sarah Murdoch, Ryoichi Saito, Elaina Collie–Duguid, Shirley Richardson, Simon L. Priestnall, Joan Wilson, Mahalakshmi Gurumurthy, Justine Royle, Leslie Samuel, George Ramsay, Katherine A. Vallis, Kevin R. Foster, James McCullagh, Anne E. Kiltie
Abstract
BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.