Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
Int J Cancer. 2019 Nov 15;145(10):2701-2711. doi: 10.1002/ijc.32339. Epub 2019 May 10.
Overuse of antibiotic drugs alters the composition of gut microbiota and has detrimental effects on the host. In our study, we investigated association of gut flora and antibiotics in the prognosis of patients with liver cancer who have undergone chemotherapy by analyzing two independent clinical studies. We retrospectively subanalyzed a previously reported randomized controlled trial (RCT) on hepatic arterial infusion chemotherapy in patients with hepatocellular carcinoma (HCC) to investigate the association between use of antibiotics and prognosis. In the other study, we prospectively determined the abundance of specific bacterial genus in patients with HCC by sequencing 16S ribosomal RNA and assessed its association with survival. Subanalysis of the RCT data showed that, of 26 types of antibiotics used, administration of carbapenem before or during chemotherapy was associated with poor progression-free survival (PFS) and overall survival (OS) of patients with HCC (carbapenem + vs. -; median PFS, 78 days vs. 154 days, p = 0.0053; median OS, 177 days vs. 475 days, p = 0.0003). Multivariate analysis revealed that antianaerobic drug use is an independent predictor of poor prognosis. In the prospective study, the abundance of Blautia in fecal microbiota correlated positively with both PFS and OS of patients with HCC who underwent chemotherapy. Use of antibiotics targeting anaerobes is associated with a poor prognosis in patients with HCC who have undergone chemotherapy, whereas the intestinal anaerobic bacteria, Blautia is associated with a good prognosis. These findings might indicate the need for caution regarding overuse of broad-spectrum antibiotics targeting anaerobes in patients with HCC.
过度使用抗生素会改变肠道菌群的组成，并对宿主产生不利影响。在我们的研究中，我们通过分析两项独立的临床研究，调查了肠道菌群与接受化疗的肝癌患者的抗生素之间的关联。我们回顾性地对先前报道的肝细胞癌患者肝动脉灌注化疗的随机对照试验（RCT）进行了亚分析，以研究抗生素的使用与预后之间的关系。在另一项研究中，我们通过测序 16S 核糖体 RNA 前瞻性地确定了 HCC 患者特定细菌属的丰度，并评估了其与生存的关系。RCT 数据的亚分析表明，在 26 种使用的抗生素中，化疗前或化疗期间使用碳青霉烯类抗生素与 HCC 患者的无进展生存期（PFS）和总生存期（OS）较差相关（碳青霉烯类+与-；中位 PFS，78 天与 154 天，p=0.0053；中位 OS，177 天与 475 天，p=0.0003）。多变量分析显示，使用抗厌氧菌药物是预后不良的独立预测因素。在前瞻性研究中，粪便微生物群中 Blautia 的丰度与接受化疗的 HCC 患者的 PFS 和 OS 均呈正相关。在接受化疗的 HCC 患者中，使用针对厌氧菌的抗生素与预后不良相关，而肠道厌氧菌 Blautia 与良好的预后相关。这些发现可能表明需要谨慎使用针对 HCC 患者的广谱抗厌氧菌抗生素。
