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
{"title":"Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Result: </strong>Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8<sup>+</sup> 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.</p><p><strong>Conclusion: </strong>These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8000,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092108/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbiome","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s40168-024-01804-1","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.