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

IF 13.8 1区 生物学 Q1 MICROBIOLOGY
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
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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.

补充膳食纤维可增强放疗对肿瘤的控制并减轻肠道辐射毒性。
背景:采用无毒方法提高放疗效果是有益的,尤其是在老龄人群中。临床前研究结果表明,高纤维饮食可通过改变肠道微生物群使膀胱肿瘤对照射敏感,同时临床证据表明益生元可增强抗癌免疫力,基于此,我们假设膳食纤维及其肠道微生物群的改变可通过分泌代谢物和/或免疫调节使肿瘤放射敏感。我们研究了高纤维饮食与辐照相结合对免疫缺陷的 C57BL/6 小鼠膀胱癌侧腹异体移植的疗效:结果:与 0.2% 纤维素相比,车前子加菊粉能显著缩小肿瘤大小,延缓照射后肿瘤的生长,并能提高肿瘤内 CD8+ 细胞。辐照后,肿瘤控制与漆树梭菌科的丰度呈正相关。车前子加抗性淀粉可使肿瘤放射增敏,与乳酸菌属丰度和盲肠异阿魏酸水平的增加呈正相关,与肿瘤控制方面的有利反应相关。车前子加菊粉减轻了 14 Gy 造成的急性辐射损伤。车前子加菊粉提高了盲肠中乙酸盐、丁酸盐和丙酸盐的水平,而单独使用车前子和车前子加抗性淀粉则提高了乙酸盐的水平。人类肠道微生物菌群在菌门水平上一般更像小鼠 0.2% 纤维素菌群,而不是高纤维菌群:结论:这些补充剂在盆腔恶性肿瘤患者中与放疗结合使用可能会有帮助。视频摘要
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来源期刊
Microbiome
Microbiome MICROBIOLOGY-
CiteScore
21.90
自引率
2.60%
发文量
198
审稿时长
4 weeks
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.
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