Abstract

Antibiotics (ATBs) induce dysbiosis of the gut microbiota by altering the diversity and composition of the microbiota, which mediates the efficacy and toxicity of cancer therapy. The influence of dysbiosis induced by ATB administration on primary resistance to chemotherapy in patients with advanced gastric cancer (GC) has been rarely studied. We evaluated the effect of ATB administration on chemotherapy efficacy in patients with advanced GC. Patients with GC were divided into two groups according to the status of ATB administration: ATB-treated and control groups. Tumor responses, progression-free survival (PFS) and overall survival (OS) were assessed. We found that the incidence of progressive disease in the ATB-treated group was significantly higher when compared with that in the control group that received no ATB treatment (72.73% vs. 29.55%, p = 0.007). In addition, ATB administration was associated with shorter PFS [median PFS: 1.47 vs. 4.97 months, hazard ratio (HR): 2.296, 95% confidence interval (CI): 1.214 − 4.342, p = 0.011] and reduced OS (median OS: 9.97 vs. 13.3 months, HR: 2.101, 95% CI: 1.030 − 4.286, p = 0.041) based on univariate analysis. Subsequent multivariate analysis also indicated that ATB administration was an independent prognostic factor for PFS (HR: 3.361, 95% CI: 1.592 − 7.097, p = 0.001) and OS (HR: 2.280, 95% CI: 1.042 − 4.991, p = 0.039). ATB administration is associated with reduced chemotherapy efficacy and poor prognosis in patients with advanced GC. Modulations in ATB-related dysbiosis and gut microbiota composition improve the clinical outcomes of chemotherapy.

Supplemental data for this article is available online at https://dx.doi.org/10.1080/13102818.2021.1953400 .

摘要

抗生素 (ATB) 通过改变微生物群的多样性和组成来诱导肠道微生物群的生态失调，从而调节癌症治疗的疗效和毒性。很少研究 ATB 给药引起的生态失调对晚期胃癌 (GC) 患者对化疗的原发性耐药的影响。我们评估了 ATB 给药对晚期 GC 患者化疗疗效的影响。GC 患者根据 ATB 给药状态分为两组：ATB 治疗组和对照组。评估了肿瘤反应、无进展生存期（PFS）和总生存期（OS）。我们发现，与未接受 ATB 治疗的对照组相比，ATB 治疗组的疾病进展发生率显着更高（72.73% vs. 29.55%，p  = 0.007）。此外，ATB 给药与较短的 PFS [中位 PFS：1.47 与 4.97 个月，风险比 (HR)：2.296，95% 置信区间 (CI)：1.214 - 4.342，p  = 0.011] 和降低的 OS（中位 OS ：9.97 与 13.3 个月，HR：2.101，95% CI：1.030 - 4.286，p  = 0.041）基于单变量分析。随后的多变量分析还表明，ATB给药是为PFS的独立预后因素（HR：3.361，95％CI：1.592 - 7.097，p  = 0.001）和OS（HR：2.280，95％CI：1.042 - 4.991，p = 0.039）。ATB 给药与晚期 GC 患者的化疗疗效降低和预后不良有关。ATB 相关生态失调和肠道微生物群组成的调节可改善化疗的临床结果。

本文的补充数据可在 https://dx.doi.org/10.1080/13102818.2021.1953400 在线获得。