一线化疗对肺癌患者肠道菌群的影响

The effect of first⁃line chemotherapy on the intestinal flora of patients with lung cancer

目的探讨化疗对原发性肺癌患者肠道菌群及其信号通路的影响。方法纳入2019年2月至7月首次接受化疗的26例原发性肺癌患者,采集化疗前48~72 h内化疗前(CBG)组和第2个周期化疗后至第3个周期前化疗后(CAG)组新鲜粪便样本。利用IlluminaMiSeq高通量测序平台对粪便标本中肠道微生物的16S rRNA基因进行测序,使用QIIME 2.0处理测序数据并分析肠道微生物丰富度和多样性,通过PICRUSt预测肠道微生物群的功能特征。结果与CAG组比,CBG组肠道菌丰富度高,但两组菌群多样性差异无统计学意义(P>0.05);患者肠道菌群组成方面,CBG组和CAG组有4个共同的优势菌门,包括厚壁菌门、拟杆菌门、变形菌门和放线菌门。而在菌属组成上CBG组的粪杆菌属、颤螺旋菌属和另枝菌属显著降低,而韦永氏球菌属、链球菌属和Christensenellaceae科一种未分类菌属(f_Christensenellaceae_uncl.)显著升高(P<0.05)。功能代谢方面探索发现,CAG组肠道微生物群代谢类型出现脂肪酸代谢、色氨酸代谢、糖酵解等功能上调。结论原发性肺癌患者首次接受化疗2个周期后,肠道条件致病菌增加而产丁酸盐菌属下降,并且出现促肿瘤发展及耐药代谢途径和炎症相关代谢途径上调的现象。提示患者肠道黏膜受损不易恢复,肠屏障功能下降。

Objective To investigate the effect of chemotherapy on the intestinal flora and signaling pathways in patients with primary lung cancer.Methods 26 patients with primary lung cancer who received chemotherapy for the first time from February 2019 to July 2019 were enrolled,and fresh stool samples were collected within 48 to 72 hours before chemotherapy(CBG group)and after the second cycle of chemotherapy(CAG group).The Illumina MiSeq high⁃throughput sequencing platform was used to sequence the 16S rRNA genes of gut microbes in fecal specimens.QIIME 2.0 was used to process the sequencing data and to predict the functional characteristics of the gut microbiota through PICRUST.Results Compared with the CAG group,the CBG group had higher intestinal bacteria richness,but the difference in the diversity of the two groups of bacteria was not statistically significant(P>0.05),in terms of the composition of intestinal flora,the CBG and CAG groups had four common phylum of superior bacteria includes Firmicutes,Bacteroidetes,Proteobacteria and Actinobacteria(P<0.05).The genus composition of CBG group Faecalibacterium,Oscillospira and Alipipes were significantly reduced,while Veillonella,Streptococcus and f_Christensenellaceae_uncl.were significantly increased.In terms of functional metabolism,it was found that the metabolic type of the intestinal microbiota in the CAG group was up⁃regulated in fatty acid metabolism,tryptophan metabolism,glycolysis and other functions.Conclusion After the first two cycles of chemotherapy for patients with primary lung cancer,the pathogenic bacteria in the intestinal condition increased while the butyrate⁃producing bacteria decreased.The tumor⁃promoting,drug⁃resistant metabolic pathways and inflammation⁃related metabolic pathways were up⁃regulated.It is suggested that the damage of the intestinal mucosa is not easy to recover,and the function of intestinal barrier is decreased.