Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Biomedicum kvarter 8A. Solnavägen 9, SE-171 65, Stockholm, Sweden.
Science for Life Laboratory (SciLifeLab), SE-171 21, Stockholm, Sweden.
Br J Cancer. 2020 Dec;123(12):1825-1832. doi: 10.1038/s41416-020-01082-2. Epub 2020 Sep 24.
It is understudied whether the posed association of oral antibiotics with colorectal cancer (CRC) varies between antibiotic spectrums, colorectal continuum, and if a non-linear dose-dependent relationship is present.
Three electronic databases and a trial platform were searched for all relevant studies, from inception until February 2020, without restrictions. Random-effects meta-analyses provided pooled effect-sizes (ES) with 95% confidence intervals (CI). Dose-response analyses modelling the relationship between number of days exposed to antibiotics and CRC risk were extended to non-linear multivariable random-effects models.
Of 6483 identified publications ten were eligible, including 4.1 million individuals and over 73,550 CRC cases. The pooled CRC risk was increased among individuals who ever-used antibiotics (ES = 1.17, 95%CI 1.05-1.30), particularly for broad-spectrum antibiotics (ES = 1.70, 95%CI 1.26-2.30), but not for narrow-spectrum antibiotic (ES = 1.11, 95% 0.93-1.32). The dose-response analysis did not provide strong evidence of any particular dose-response association, and the risk patterns were rather similar for colon and rectal cancer.
The antibiotic use associated CRC risk seemingly differs between broad- and narrow-spectrum antibiotics, and possibly within the colorectal continuum. It remains unclear whether this association is causal, requiring more mechanistic studies and further clarification of drug-microbiome interactions.
口服抗生素与结直肠癌（CRC）之间的关联是否因抗生素谱、结直肠连续体的不同而不同，以及是否存在非线性剂量依赖性关系，这方面的研究还很不足。
从研究开始到 2020 年 2 月，在三个电子数据库和一个试验平台上搜索了所有相关研究，没有任何限制。随机效应荟萃分析提供了汇总的效应大小（ES）及其 95%置信区间（CI）。对暴露于抗生素的天数与 CRC 风险之间的关系进行剂量反应分析，并扩展到非线性多变量随机效应模型。
在 6483 篇已识别的文献中，有 10 篇符合条件，包括 410 万人和超过 73550 例 CRC 病例。与从未使用过抗生素的人相比，曾经使用过抗生素的人患 CRC 的风险增加（ES=1.17，95%CI 1.05-1.30），特别是广谱抗生素（ES=1.70，95%CI 1.26-2.30），但窄谱抗生素（ES=1.11，95%CI 0.93-1.32）没有增加风险。剂量反应分析并没有提供任何特定剂量反应关联的有力证据，而且结肠癌和直肠癌的风险模式非常相似。
抗生素使用与 CRC 风险之间的关联似乎在广谱和窄谱抗生素之间以及结直肠连续体中存在差异。目前尚不清楚这种关联是否具有因果关系，需要更多的机制研究和对药物-微生物组相互作用的进一步澄清。
