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

Chee Kin Then; Salome Paillas; Aliu Moomin; Mariya D Misheva; Rachel A Moir; Susan M Hay; David Bremner; Kristine S Roberts Nee Nellany; Ellen E Smith; Zeynab Heidari; Daniel Sescu; Xuedan Wang; Alejandro Suárez-Bonnet; Nadine Hay; Sarah L Murdoch; Ryoichi Saito; Elaina S R Collie-Duguid; Shirley Richardson; Simon L Priestnall; Joan M Wilson; Mahalakshmi Gurumurthy; Justine S Royle; Leslie M Samuel; George Ramsay; Katherine A Vallis; Kevin R Foster; James S O McCullagh; Anne E Kiltie

doi:10.1186/s40168-024-01804-1

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

Microbiome. 2024 May 14;12(1):89. doi: 10.1186/s40168-024-01804-1.

Authors

Chee Kin Then^{1

2}, Salome Paillas¹, Aliu Moomin^{3

4}, Mariya D Misheva^{5

6}, Rachel A Moir⁷, Susan M Hay^{3

4}, David Bremner³, Kristine S Roberts Nee Nellany⁸, Ellen E Smith⁹, Zeynab Heidari⁹, Daniel Sescu¹⁰, Xuedan Wang^{11

12}, Alejandro Suárez-Bonnet¹³, Nadine Hay⁸, Sarah L Murdoch⁸, Ryoichi Saito^{14

15}, Elaina S R Collie-Duguid⁹, Shirley Richardson⁷, Simon L Priestnall¹³, Joan M Wilson⁸, Mahalakshmi Gurumurthy¹⁶, Justine S Royle¹⁷, Leslie M Samuel^{7

10}, George Ramsay^{10

18}, Katherine A Vallis¹, Kevin R Foster^{11

12}, James S O McCullagh⁵, Anne E Kiltie^{19

20

21

22}

Affiliations

¹ Department of Oncology, University of Oxford, Oxford, UK.
² Department of Radiation Oncology, Shunag Ho Hospital, Taipei Medical University, New Taipai City, Taiwan.
³ The Rowett Institute, University of Aberdeen, Aberdeen, UK.
⁴ Aberdeen Cancer Centre, University of Aberdeen, Aberdeen, UK.
⁵ Chemistry Research Laboratory, Department of Chemistry, Mansfield Road, University of Oxford, Oxford, UK.
⁶ Oxford Centre for Microbiome Studies, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
⁷ Department of Oncology, Aberdeen Royal Infirmary, Aberdeen, UK.
⁸ NHS Grampian Biorepository, Aberdeen Royal Infirmary, Aberdeen, UK.
⁹ Centre for Genome Enabled Biology and Medicine, School of Medicine Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
¹⁰ The School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
¹¹ Department of Biology, University of Oxford, Oxford, UK.
¹² Department of Biochemistry, University of Oxford, Oxford, UK.
¹³ Department of Pathobiology and Population Sciences, The Royal Veterinary College, London, UK.
¹⁴ Lineberger Comprehensive Cancer Centre, University of North Carolina at Chapel Hill, Chapel Hill, USA.
¹⁵ The Department of Urology, Kyoto University, Kyoto, Japan.
¹⁶ Department of Gynaecological Oncology, Aberdeen Royal Infirmary, Aberdeen, UK.
¹⁷ Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK.
¹⁸ Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
¹⁹ Department of Oncology, University of Oxford, Oxford, UK. [email protected].
²⁰ The Rowett Institute, University of Aberdeen, Aberdeen, UK. [email protected].
²¹ Aberdeen Cancer Centre, University of Aberdeen, Aberdeen, UK. [email protected].
²² The School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK. [email protected].

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. Video Abstract.

Keywords: Cancer; Dietary fibre; Gut microbiota; Immunomodulation; Isoferulic acid; Radiotherapy; Short-chain fatty acids.

MeSH terms

Animals
CD8-Positive T-Lymphocytes
Dietary Fiber*
Dietary Supplements*
Female
Gastrointestinal Microbiome* / drug effects
Humans
Intestines / microbiology
Intestines / radiation effects
Inulin* / administration & dosage
Mice
Mice, Inbred C57BL*
Psyllium*
Radiation Injuries / prevention & control
Urinary Bladder Neoplasms* / pathology
Urinary Bladder Neoplasms* / radiotherapy