Patients with pelvic malignancies often receive radiosensitising chemotherapy with radiotherapy to improve survival; however, this is at the expense of increased normal tissue toxicity, particularly in elderly patients. Here, we explore if an alternative, low-cost, and non-toxic approach can achieve radiosensitisation in mice transplanted with human bladder cancer cells. Other investigators have shown slower growth of transplanted tumours in mice fed high-fibre diets. We hypothesised that mice fed a high-fibre diet would have improved tumour control following ionising radiation (IR) and that this would be mediated through the gut microbiota. We investigated the effects of four different diets (low-fibre, soluble high-fibre, insoluble high-fibre, and mixed soluble/insoluble high-fibre diets) on tumour growth in immunodeficient mice implanted with human bladder cancer flank xenografts and treated with ionising radiation, simultaneously investigating the composition of their gut microbiomes by 16S rRNA sequencing. A significantly higher relative abundance of Bacteroides acidifaciens was seen in the gut (faecal) microbiome of the soluble high-fibre group, and the soluble high-fibre diet resulted in delayed tumour growth after irradiation compared to the other groups. Within the soluble high-fibre group, responders to irradiation had significantly higher abundance of B. acidifaciens than non-responders. When all mice fed with different diets were pooled, an association was found between the survival time of mice and relative abundance of B. acidifaciens. The gut microbiome in responders was predicted to be enriched for carbohydrate metabolism pathways, and in vitro experiments on the transplanted human bladder cancer cell line suggested a role for microbial-generated short-chain fatty acids and/or other metabolites in the enhanced radiosensitivity of the tumour cells. Soluble high-fibre diets sensitised tumour xenografts to irradiation, and this phenotype was associated with modification of the microbiome and positively correlated with B. acidifaciens abundance. Our findings might be exploitable for improving radiotherapy response in human patients.

中文翻译：

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酸性拟杆菌的相对丰度与高纤维饮食相关的放射增敏作用相关。

盆腔恶性肿瘤患者经常接受放射增敏化学疗法和放射疗法以提高生存率。然而，这是以增加正常组织毒性为代价的，特别是在老年患者中。在这里，我们探讨了一种替代的，低成本且无毒的方法是否可以在移植了人膀胱癌细胞的小鼠中实现放射增敏作用。其他研究人员显示，高纤维饮食的小鼠中移植瘤的生长较慢。我们假设喂高纤维饮食的小鼠在电离辐射（IR）后可改善肿瘤控制，并且这将通过肠道菌群介导。我们调查了四种不同饮食（低纤维，可溶性高纤维，不溶性高纤维，以及混合的可溶性/不溶性高纤维饮食）对植入人膀胱癌侧翼异体移植物并经电离辐射治疗的免疫缺陷小鼠的肿瘤生长的影响，同时通过16S rRNA测序研究其肠道微生物组的组成。在可溶性高纤维组的肠道（粪便）微生物组中发现了酸性拟杆菌的相对丰度较高，与其他组相比，可溶性高纤维饮食在辐射后导致肿瘤生长延迟。在可溶性高纤维组中，对辐射的响应者比其他响应者的酸性芽孢杆菌含量更高。当汇集所有用不同饮食喂养的小鼠时，发现小鼠的存活时间与酸双歧杆菌的相对丰度之间存在关联。预测应答者中的肠道微生物组富含碳水化合物的代谢途径，并且在移植的人膀胱癌细胞系上进行的体外实验表明，微生物产生的短链脂肪酸和/或其他代谢物在增强小鼠的放射敏感性方面具有重要作用。肿瘤细胞。可溶性高纤维饮食使肿瘤异种移植物对放射线敏感，这种表型与微生物组的修饰有关，并且与酸双歧杆菌的丰度呈正相关。我们的发现可能可用于改善人类患者的放射治疗反应。在移植的人膀胱癌细胞系上进行的体外实验表明，微生物产生的短链脂肪酸和/或其他代谢产物在增强肿瘤细胞的放射敏感性方面具有重要作用。可溶性高纤维饮食使肿瘤异种移植物对放射线敏感，这种表型与微生物组的修饰有关，并且与酸双歧杆菌的丰度呈正相关。我们的发现可能可用于改善人类患者的放射治疗反应。在移植的人膀胱癌细胞系上进行的体外实验表明，微生物产生的短链脂肪酸和/或其他代谢产物在增强肿瘤细胞的放射敏感性方面具有重要作用。可溶性高纤维饮食使肿瘤异种移植物对放射线敏感，这种表型与微生物组的修饰有关，并且与酸双歧杆菌的丰度呈正相关。我们的发现可能可用于改善人类患者的放射治疗反应。