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化疗诱导的结直肠癌相关肠道微生物群抑制及宿主微小RNA表达的调节。

Chemotherapy-induced suppression of colorectal cancer-associated gut microbiota and modulation of host miRNA expression.

作者信息

Wang Chunli, Kuang Baoyang, Yang Kuan, Xiao Xuewen, Wu Caixia, Li An, Zeng Xiaoli, Wang Xiangcai, Ye Jianming

机构信息

Intensive Care Unit, First Affiliated Hospital, Gannan Medical University Ganzhou 341000, Jiangxi, China.

Department of Oncology, First Affiliated Hospital, Gannan Medical University Ganzhou 341000, Jiangxi, China.

出版信息

Am J Transl Res. 2025 Aug 15;17(8):6573-6586. doi: 10.62347/XXCS3377. eCollection 2025.

Abstract

OBJECTIVES

To characterize gut microbiome alterations in colorectal cancer (CRC) patients following cancer chemotherapy (CCT) and to explore associations with bacterial translocation and host miRNA dynamics.

METHODS

Stool samples were prospectively collected from 20 CRC patients who had undergone radical surgery followed by adjuvant chemotherapy (CAPOX/mFOLFOX6). Stool samples were collected pre- and post-CCT. Microbial profiling was performed using 16S rRNA sequencing. Bacterial translocation was assessed by measuring serum anti-Lipopolysaccharides (LPS) IgA/IgG levels by ELISA. miRNA expression of miR-143 and miR-145 was quantified using qPCR.

RESULTS

Post-CCT samples showed significant increases in gut microbiome diversity (<0.05), with higher relative abundances of and , and decreased abundances of and (P<0.005). Network analysis identified and as possible CRC-associated taxa. Serum anti-LPS IgA and IgG levels significantly declined post-CCT, indicating reduced bacterial translocation. Concurrently, miR-143 and miR-145 levels increased more than twofold post-CCT (P<0.01), positively correlating with microbial shifts.

CONCLUSION

CCT induces significant remodeling of CRC-associated gut microbiota, characterized by suppression of pathogenic genera and enrichment of pro-inflammatory taxa. These changes align with reduced bacterial translocation and increased expression of tumor-suppressive miRNAs, suggesting that CCT exerts dual therapeutic effects by simultaneously modulating microbial communities and host molecular pathways.

摘要

目的

描述接受癌症化疗(CCT)的结直肠癌(CRC)患者肠道微生物群的变化,并探讨其与细菌易位和宿主微小RNA(miRNA)动态变化的关联。

方法

前瞻性收集20例接受根治性手术并随后接受辅助化疗(CAPOX/mFOLFOX6)的CRC患者的粪便样本。在CCT前后收集粪便样本。使用16S rRNA测序进行微生物谱分析。通过酶联免疫吸附测定(ELISA)测量血清抗脂多糖(LPS)IgA/IgG水平来评估细菌易位。使用定量聚合酶链反应(qPCR)对miR-143和miR-145的miRNA表达进行定量。

结果

CCT后样本显示肠道微生物群多样性显著增加(<0.05), 和 的相对丰度更高,而 和 的丰度降低(P<0.005)。网络分析确定 和 为可能与CRC相关的分类群。CCT后血清抗LPS IgA和IgG水平显著下降,表明细菌易位减少。同时,CCT后miR-143和miR-145水平增加了两倍多(P<0.01),与微生物变化呈正相关。

结论

CCT诱导与CRC相关的肠道微生物群发生显著重塑,其特征是致病属的抑制和促炎分类群的富集。这些变化与细菌易位减少和肿瘤抑制性miRNA表达增加一致,表明CCT通过同时调节微生物群落和宿主分子途径发挥双重治疗作用。

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