肠道微生物群在接受卡培他滨治疗的转移性结直肠癌患者中的作用
The Role of Intestinal Microbiota in Metastatic Colorectal Cancer Patients Treated With Capecitabine.
作者信息
Aarnoutse Romy, Ziemons Janine, de Vos-Geelen Judith, Valkenburg-van Iersel Liselot, Wildeboer Aurelia C L, Vievermans Anne, Creemers Geert-Jan M, Baars Arnold, Vestjens Hanneke J H M J, Le Giang N, Barnett David J M, Rensen Sander S, Penders John, Smidt Marjolein L
机构信息
GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Internal Medicine, Division of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands.
出版信息
Clin Colorectal Cancer. 2022 Jun;21(2):e87-e97. doi: 10.1016/j.clcc.2021.10.004. Epub 2021 Oct 17.
BACKGROUND
Previous pre-clinical research has indicated that the intestinal microbiota can potentiate anti-tumour efficacy of capecitabine and that capecitabine treatment impacts intestinal microbiota composition and diversity. Using a longitudinal design, this study explores the associations between the intestinal microbiota and treatment response in patients with metastatic colorectal cancer (mCRC) during capecitabine treatment.
PATIENTS AND METHODS
Patients with mCRC treated with capecitabine were prospectively enrolled in a multicentre cohort study. Patients collected a faecal sample and completed a questionnaire before, during, and after three cycles of capecitabine. Several clinical characteristics, including tumour response, toxicity and antibiotic use were recorded. Intestinal microbiota were analysed by amplicon sequencing of the 16S rRNA V4 gene-region.
RESULTS
Thirty-three patients were included. After three cycles of capecitabine, six patients (18%) achieved a partial response, 25 (76%) showed stable disease, and one (3%) experienced progressive disease. Of the 90 faecal samples were collected. Microbial diversity (α-diversity), community structure (β-diversity), and bacterial abundance on phylum and genus level were not significantly different between responders and non-responders and were not significantly affected by three cycles of capecitabine.
CONCLUSION
This is the first clinical study with longitudinal intestinal microbiota sampling in mCRC patients that explores the role of the intestinal microbiota during treatment with capecitabine. Intestinal microbiota composition and diversity before, during, and after three cycles of capecitabine were not associated with response in this study population. Capecitabine did not induce significant changes in the microbiota composition and diversity during the treatment period. Individual effects of antibiotics during capecitabine treatment were observed.
背景
先前的临床前研究表明，肠道微生物群可增强卡培他滨的抗肿瘤疗效，且卡培他滨治疗会影响肠道微生物群的组成和多样性。本研究采用纵向设计，探讨转移性结直肠癌（mCRC）患者在卡培他滨治疗期间肠道微生物群与治疗反应之间的关联。
患者与方法
接受卡培他滨治疗的mCRC患者被前瞻性纳入一项多中心队列研究。患者在卡培他滨三个周期治疗前、治疗期间和治疗后收集粪便样本并完成一份问卷。记录了包括肿瘤反应、毒性和抗生素使用在内的若干临床特征。通过对16S rRNA V4基因区域进行扩增子测序分析肠道微生物群。
结果
纳入33例患者。卡培他滨三个周期治疗后，6例患者（18%）达到部分缓解，25例（76%）疾病稳定，1例（3%）疾病进展。共收集了90份粪便样本。应答者与非应答者之间的微生物多样性（α-多样性）、群落结构（β-多样性）以及门和属水平的细菌丰度无显著差异，且未受到卡培他滨三个周期治疗的显著影响。
结论
这是第一项对mCRC患者进行纵向肠道微生物群采样的临床研究，旨在探讨肠道微生物群在卡培他滨治疗期间的作用。在本研究人群中，卡培他滨三个周期治疗前、治疗期间和治疗后肠道微生物群的组成和多样性与反应无关。在治疗期间，卡培他滨未引起微生物群组成和多样性的显著变化。观察到了卡培他滨治疗期间抗生素的个体效应。
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