一线化疗联合免疫治疗对晚期肺癌患者肠道菌群影响及与胃肠道毒副反应的关系

Impact of first-line chemotherapy combined with immunotherapy on the gut microbiota of patients with advanced lung cancer and its relationship with gastrointestinal toxicities

目的探讨晚期肺癌患者接受一线化疗联合免疫疗法治疗前后的胃肠道菌群变化及与患者胃肠道毒副反应程度的关系。方法选择2020年1月—2022年6月本院确诊的122例晚期肺癌患者的临床资料进行回顾性分析。所有患者均在本院接受一线化疗联合免疫疗法治疗。对比患者治疗前后的肠道菌群数量、粪便中的分泌型免疫球蛋白A(sIgA)的差异,并按照美国国立癌症研究所NCI常见不良反应事件评价标准(CTCAE4.0)将患者分为轻度、中重度进行分层统计分析。结果122例患者,经过一线化疗及免疫学治疗,患者治疗后的普拉梭菌、肠球菌、乳酸菌、双歧杆菌、类杆菌-普氏菌组、柔嫩梭菌、肠杆菌、普氏菌组、梭菌组1、梭菌组2、梭状芽孢杆菌簇ⅪⅤa、sIgA水平菌均较治疗前显著降低,差异具有统计学意义(P<0.05)。122例患者,化疗过程中,轻度胃肠道反应患者67例、中度胃肠道反应患者48例、重度胃肠道反应患者7例,轻度组和中重度组患者的年龄、BMI、WHR、性别、吸烟、合并疾病、TNM分期、病理学类型比较,差异均不具有统计学意义(P>0.05)。化疗之后,中重度组患者的普拉梭菌、肠球菌、乳酸菌、双歧杆菌、类杆菌-普氏菌组、柔嫩梭菌、肠杆菌、普氏菌组、梭菌组2、梭菌组4、Ⅳ群瘤胃球菌、链球菌、sIgA水平菌均显著低于轻度组患者,差异具有统计学意义(P<0.05)。结论晚期肺癌一线化疗联合免疫疗法治疗后胃肠道菌群明显失衡,胃肠道毒副反应越严重患者的胃肠道菌群失衡越严重。

Objective To investigate the changes in gastrointestinal microbiota and their relationship with the severity of gastrointestinal toxicities in patients with advanced lung cancer before and after first-line chemotherapy combined with immunotherapy.Methods A retrospective analysis was conducted on the clinical data of 122 patients with advanced lung cancer diagnosed at our hospital from January 2020 to June 2022.All patients received first-line chemotherapy combined with immunotherapy in our hospital.The differences in number of Gut microbiota and the secretory immunoglobulin A(sIgA)in stool before and after chemotherapy were compared.According to the National Cancer Institute(NCI)Common Terminology Criteria for Adverse Events(CTCAE4.0),patients were divided into mild and moderate to severe subgroup for stratified statistical analysis.Results 122 patients were treated with first-line chemotherapy and immunology.After treatment,the levels of Faecalibacterium prausnitzii,Enterococcus,Lactobacillus,Bifidobacterium,Bacteroid Pryotella group,Clostridium tenella,Enterobacter,Pryotella group,Clostridium group 1,Clostridium group 2,Clostridium cluster XIⅤa,sIgA were significantly lower than those before treatment(P<0.05).Among the 122 patients,67 experienced mild gastrointestinal reactions,48 moderate,and 7 severe during chemotherapy.There were no statistically significant differences in age,BMI,WHR,gender,smoking status,comorbidities,TNM staging,and pathological types between the mild and moderate-to-severe groups(P>0.05).Post-chemotherapy,the levels of Faecalibacterium prausnitzii,Enterococcus,Lactobacillus,Bifidobacterium,Bacteroides-Prevotella group,Clostridium leptum,Enterobacteriaceae,Prevotella group,Clostridium clusterⅡ,Clostridium clusterⅣ,and sIgA in the moderate-to-severe group were significantly lower than in the mild group(P<0.05).Conclusions There is an obvious imbalance of gastrointestinal flora in patients with advanced lung cancer after first-line chemotherapy combined with immunotherapy,and the imbalance of gastrointestinal flora is more serious in patients with gastrointestinal toxicity getting worse.