Emoto Shigenobu, Inoue Ryo, Murai Shin, Inagaki Yuriko, Nozawa Hiroaki, Sasaki Kazuhito, Murono Koji, Kaneko Kensuke, Yokoyama Yuichiro, Abe Shinya, Nagai Yuzo, Shinagawa Takahide, Tachikawa Yuichi, Okada Satoshi, Tsukahara Takamitsu, Ohashi Kai, Ohno Masashi, Andoh Akira, Ishihara Soichiro
Department of Surgical Oncology, University of Tokyo, Tokyo, Japan.
Laboratory of Animal Science, Setsunan University, Hirakata, Japan.
Colorectal Dis. 2025 May;27(5):e70106. doi: 10.1111/codi.70106.
Preoperative chemoradiotherapy (CRT) is administered for locally advanced rectal cancer (LARC); however, its efficacy and toxicity vary among patients. This study aimed to elucidate the relationship between the gut microbiota and the effectiveness and adverse events of CRT.
This prospective study included 21 patients with LARC with no history of antibiotic or probiotic administration for 6 months. Tumour mucosa, non-tumour mucosa and faecal samples were collected before and after CRT, and bacterial DNA was extracted. Metataxonomic analysis targeting the V3 and V4 regions of the 16S rRNA gene was conducted to determine the diversity and composition of the microbiota. Linear discriminant analysis effect size (LEfSe) was used to explore potential bacterial taxa predicting pathological complete response (pCR) and treatment-associated diarrhoea, which are major adverse events of CRT.
Among the 21 patients, five achieved pCR and seven experienced severe treatment-associated diarrhoea. There were no significant differences in α-diversity and β-diversity of the microbiota between the groups at any sampling sites before or after CRT. Exploratory analysis using LEfSe identified Peptostreptococcus, Coprococcus and Phoceaicola in the tumour mucosa before CRT as significant indicators for achieving pCR. Additionally, Collinsella, Haemophilus and Desulfovibrionaceae are associated with treatment-associated diarrhoea. Microbiome composition changed before and after CRT, with a notable decrease in the genus Fusobacterium_C and other taxa. β-diversity in the tumour area also changed significantly (P = 0.03).
This study suggests an association between the gut microbiota, the therapeutic effectiveness of CRT and the occurrence of treatment-associated diarrhoea in rectal cancer. These results indicate the potential for predicting treatment efficacy and adverse events based on the microbiota composition.
术前放化疗（CRT）用于局部晚期直肠癌（LARC）；然而，其疗效和毒性在患者之间存在差异。本研究旨在阐明肠道微生物群与CRT有效性及不良事件之间的关系。
这项前瞻性研究纳入了21例LARC患者，这些患者在6个月内没有使用抗生素或益生菌的历史。在CRT前后收集肿瘤黏膜、非肿瘤黏膜和粪便样本，并提取细菌DNA。针对16S rRNA基因的V3和V4区域进行宏分类分析，以确定微生物群的多样性和组成。使用线性判别分析效应大小（LEfSe）来探索预测病理完全缓解（pCR）和治疗相关腹泻的潜在细菌类群，这两者是CRT的主要不良事件。
21例患者中，5例达到pCR，7例经历了严重的治疗相关腹泻。在CRT前后的任何采样部位，各分组之间微生物群的α多样性和β多样性均无显著差异。使用LEfSe进行的探索性分析确定，CRT前肿瘤黏膜中的消化链球菌、粪球菌和海栖菌属是实现pCR的重要指标。此外，柯林斯菌属、嗜血杆菌属和脱硫弧菌科与治疗相关腹泻有关。CRT前后微生物群组成发生变化，梭杆菌属_C和其他类群显著减少。肿瘤区域的β多样性也发生了显著变化（P = 0.03）。
本研究表明肠道微生物群、CRT的治疗效果与直肠癌治疗相关腹泻的发生之间存在关联。这些结果表明基于微生物群组成预测治疗效果和不良事件的潜力。
