Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity

Then, CK; Paillas, S; Moomin, A; Misheva, MD; Moir, RA; Hay, SM; Bremner, D; Roberts, KS; Smith, EE; Heidari, Z; Sescu, D; Wang, XD; Suárez-Bonnet, A; Hay, N; Murdoch, SL; Saito, R; Collie-Duguid, ESR; Richardson, S; Priestnall, SL; Wilson, JM; Gurumurthy, M; Royle, JS; Samuel, LM; Ramsay, G; Vallis, KA; Foster, KR; McCullagh, JSO; Kiltie, AE

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 Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ 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. C3P3Z-i-BEWcsPG8U_9P4f Video AbstractConclusion These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. C3P3Z-i-BEWcsPG8U_9P4f Video Abstract

Citation

Then, C., Paillas, S., Moomin, A., Misheva, M., Moir, R., Hay, S., Bremner, D., Roberts, K., Smith, E., Heidari, Z., Sescu, D., Wang, X., Suárez-Bonnet, A., Hay, N., Murdoch, S., Saito, R., Collie-Duguid, E., Richardson, S., Priestnall, S., Wilson, J., …Kiltie, A. (2024). Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity. Microbiome, 12(1), https://doi.org/10.1186/s40168-024-01804-1

• Journal Article Type: Article
• Acceptance Date: Apr 2, 2024
• Online Publication Date: May 14, 2024
• Publication Date: 2024
• Deposit Date: Jun 4, 2024
• Publicly Available Date: Jun 4, 2024
• Print ISSN: 2049-2618
• Electronic ISSN: 2049-2618
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 1
• DOI: https://doi.org/10.1186/s40168-024-01804-1
• Keywords: Radiotherapy; Dietary fibre; Gut microbiota; Short-chain fatty acids; Isoferulic acid; Cancer; Immunomodulation; FERULIC ACID; RESISTANT STARCH; ISOFERULIC ACID; BREAST-CANCER; FATTY-ACIDS; CELLS; IMMUNOTHERAPY; INHIBITION; OLIGOFRUCTOSE; MICROBIOME