Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Anticancer Res. 2020 Feb;40(2):665-676. doi: 10.21873/anticanres.13996.
BACKGROUND/AIM: Sorafenib results in several adverse events, the mechanism and predictors of which are unknown. Recently, it was reported that metabolism by microbiome changes the structure and effects of drugs. The blood levels of sorafenib may be affected by enterohepatic recycling of sorafenib due to microbial enzymes in the gut. We evaluated the relationship between adverse events caused by sorafenib treatment and microbiome in patients with advanced hepatocellular carcinoma.
Twenty-five patients were classified into two groups based on the presence of hand-foot syndrome (HFS) or diarrhea within 12 weeks post-sorafenib treatment. Before sorafenib treatment, the fecal samples were analyzed targeting the V3-V4 region of 16s ribosomal RNA. Microbiome and predicted functional gene were compared between two groups.
The non-HFS group had a richer abundance of Veillonella, Bacillus, Enterobacter, Faecalibacterium, Lachnospira, Dialister, and Anaerostipes than the HFS group at genus level. Carotenoid biosynthesis and bacterial invasion of epithelial cells were enriched in the HFS group. The former three bacteria are classified as oral-origin bacteria, and the two predicted functions are associated with dysbiosis. The non-diarrhea group had a higher abundance of Butyricimonas and a lower abundance of Citrobacter, Peptostreptococcus, and Staphylococcaceae than the diarrhea group. Eight categories of predicted functional genes were detected with differences between the two groups.
The non-HFS group had a higher relative abundance of oral-origin bacteria, which likely led to more robust dysbiosis in the gut. This dysbiosis may affect enterohepatic recycling. Additionally, the metabolism of these short-chain fatty acids in the gut may be different between the diarrhea and non-diarrhea groups.
背景/目的：索拉非尼会引起多种不良反应，但其发生机制和预测因素尚不清楚。最近有报道称，微生物组的代谢会改变药物的结构和作用。由于肠道中的微生物酶，索拉非尼可能会通过肠肝再循环影响其血药浓度。我们评估了索拉非尼治疗引起的不良反应与晚期肝细胞癌患者微生物组之间的关系。
25 名患者根据索拉非尼治疗后 12 周内是否出现手足综合征（HFS）或腹泻分为两组。在索拉非尼治疗前，分析粪便样本 16s 核糖体 RNA 的 V3-V4 区。比较两组间微生物组和预测功能基因。
在属水平上，非 HFS 组丰度较高的菌属有韦荣球菌属、芽孢杆菌属、肠杆菌属、粪杆菌属、lachnospira 属、Dialister 属和拟杆菌属。HFS 组中富集了类胡萝卜素生物合成和细菌侵袭上皮细胞。前三种细菌被归类为口腔来源细菌，两个预测功能与肠道菌群失调有关。非腹泻组丁酸单胞菌丰度较高，柠檬酸杆菌属、消化链球菌属和葡萄球菌科属丰度较低。两组间检测到 8 类预测功能基因存在差异。
非 HFS 组中口腔来源细菌的相对丰度较高，可能导致肠道内更严重的菌群失调。这种菌群失调可能会影响肠肝再循环。此外，肠道中这些短链脂肪酸的代谢可能在腹泻和非腹泻组之间存在差异。
