化疗对胃癌术后患者肠道菌群的影响

Effects of chemotherapy on intestinal flora in patients with gastric cancer after surgery

目的:探究胃癌术后患者化疗前后肠道菌群结构差异性,寻找化疗治疗胃癌患者的肠道特异性靶标,为胃癌的治疗提供新的思路和切入点。方法:收集化疗治疗前后胃癌三期D2根治术后患者粪便标本,治疗前46例,治疗后19例,利用16S rDNA高通量测序技术研究分析化疗治疗前后肠道菌群差异性。结果:化疗后与化疗前相比,肠道菌群OTU、微生物群落构成、物种丰度、肠道菌群表型特征、GMM代谢模块、KEGG代谢途径、GBM神经递质、CAZY基因注释及EC基因注释均具有一定差异,化疗前后肠道菌群的物种多样性与物种丰富度差异无统计学意义。化疗前后在门、目、科、属、种水平上菌群物种丰度均具有显著性差异,差异菌包括d_厚壁菌门、p_厚壁菌门、Bac_丹毒丝菌目、o_丹毒丝菌目、Ery_丹毒丝菌科、f_丹毒丝菌科、f_伊格尔兹氏菌科、f_丹毒丝菌科、f_丁酸球菌科、Lac_多尔氏菌属、Lac_梭杆菌属、Lac_革兰氏阳性菌菌属、Lac_毛螺菌属_UCG-004、Lac_[瘤胃球菌]_gnavus_group菌属、丁酸杆菌菌属、Osc_普氏梭杆菌菌属、瘤胃球菌_UBA1819菌属、NK4A214_菌组、罕见小球菌属、鲸杆菌属、琼脂杆菌属、[瘤胃球菌]_gnavus_菌组、蓝绿藻菌属、毛螺菌属、s_人_肠道菌、g_链球菌、f_毛螺菌、g_蓝绿藻菌和g_经黏液真杆菌。化疗治疗前患者肠道特异菌共有5种,分别是o_丹毒丝菌、g_UBA1819、g_普氏梭杆菌、g_瘤胃球菌_gnavus_组、g_蓝绿藻菌;化疗治疗后患者肠道中特异菌发生变化,患者肠道特异菌共有5种,分别是p_厚壁菌、g_毛螺菌_UCG_001、g_梭杆菌、g_毛螺菌_UCG_004、g_多尔氏菌。结论:化疗治疗可以影响胃癌三期D2根治术后患者肠道特异菌种,这可能是化疗治疗发挥作用的途径之一。

Objective:To explore the structural differences of intestinal flora in postoperative patients with gastric cancer before and after chemotherapy treatment,and to search for gut-specific targets in the treatment of gastric cancer by chemotherapy,so as to provide new ideas and entry points for the treatment of gastric cancer.Methods:Stool samples were collected from patients with stageⅢD2 radical surgery before and after chemotherapy,including 46 cases before treatment and 19 cases after treatment.16S rDNA high-throughput sequencing technology was used to analyze the difference of intestinal flora before and after chemotherapy.Result:Compared with before chemotherapy,OTU,microbial community composition,species abundance,phenotypic characteristics of intestinal flora,GMM metabolic module,KEGG metabolic pathway,GBM neurotransmitter,CAZY gene annotation and EC gene annotation were different after chemotherapy.There was no statistically significant difference in species diversity and species richness of intestinal flora before and after chemotherapy.There were significant differences in flora species abundance at phylum,order,family,genus,and species levels before and after chemotherapy,and the differences included:d_Firmicutes,p_Firmicutes,Bac_Erysipelotrichales,o_Erysipelotrichales,Ery_Erysipelotrichaceae,f_Erysipelatoclostridiaceae,f_Eggerthellaceae,f_Erysipelotrichaceae,f_Butyricicoccaceae,Lac_Dorea,Lac_Fusicatenibacter,Lac_Lachnociostridium,Lac_Lachnospiraceae_UCG-004,Lac_[Rumlnococcus]_gnavus_group,But_Butyricicoccus,Osc_Flavonifractor,Rum_UBA1819,NK4A214_group,Subdoligranulum,Cetobacterium,Agathobacter,[Ruminococcus]_gnavus_group,Lachnoclostridium,Dorea,s_human_gut,g_Streptococcusls,f_Lachnospiraceaelg,g_Lachnoclostridiumls and g_Blautials.There were 5 types of intestinal specific bacteria in patients before chemotherapy treatment.They were o_Erysipelotrichales,g_UBA1819,g_Flavonifractor,g_Ruminococcus_gnavus_group,g_Lachnoclostridium;After chemotherapy treatment,specific bacteria in the intestinal tract of patients changed,and there were 5 types of specific bacteria in the intestinal tract of patients.They were p_Firmicutes,g_Lachnospiraceae_UCG_001,g_Fusicatenibacter,g_Lachnospiraceae_UCG_004,g_Dorea.Conclusion:Chemotherapy can affect intestinal specific bacteria in patients with gastric cancer after stageⅢD2 radical surgery,which may be one of the ways in which chemotherapy plays a role.