Abstract: Background　Chronic obstructive pulmonary disease（COPD） is a common disease characterized by persistent airflow limitation that can be prevented and treated，and chronic airway inflammation is the key to its pathogenesis.The micro-ecology of the human intestinal flora is an important guarantee for maintaining the stability of the body environment，and it can regulate the release of inflammatory mediators.At present，studies on the relationship between intestinal flora and COPD are rarely reported.Objective　To study the intestinal flora status of patients with COPD at stable phase in different groups，and to investigate the correlation between intestinal flora status and inflammatory indexes and lung function in patients with COPD at stable phase.Methods　This was a prospective cohort study of COPD at stable phase included as the observation group.The 80 patients who met the inclusion criteria at the Department of Respiratory Medicine as well as the respiratory ward of Yixing Hospital Affiliated to Jiangsu University from June 2017 to June 2018 were divided into four groups，A，B，C and D，with 20 patients in each group according to the comprehensive assessment grouping standard in Global Initiative for Chronic Obstructive Lung Disease（GOLD）（2017 report），and 20 healthy outpatients in the same period were chosen as the control group.The intestinal flora status of each group was analyzed and compared，and the correlation between intestinal flora status and inflammatory indexes and lung function in patients with COPD at stable phase were analyzed.Results　The contents of lactobacillus and bifidobacterium in group C and D were lower than those in group A，B and the control group，while the contents of enterococcus faecium and enterococcus faecalis in group C and D were significantly higher than those in group A，B and the control group（P<0.05）.The differences among interleukin-8（IL-8），interleukin-6（IL-6），tumor necrosis factor-alpha（TNF-α），endotoxin，forced expiratory volume in the first second（FEV1），forced expiratory volume in one second as percentage of predicted value（FEV1%pred） and FEV1/forced vital capacity（FEV1/FVC） in each group were statistically significant（P<0.05）．The contents of lactobacillus and bifidobacterium were negatively correlated with IL-8（r=-0.50，-0.51），IL-6（r=-0.57，-0.55），TNF-α（r=-0.57，-0.56），procalcitonin（PCT）（r=-0.27，-0.24） and ndotoxin（r=-0.76，-0.76），and positively correlated with FEV1（r=0.44，0.45），FEV1%pred（r=0.45，0.45） and FEV1/FVC（r=0.51，0.49）（P<0.05），and the contents of enterococcus faecium and enterococcus faecalis were positively correlated with IL-8（r=0.53，0.55），IL-6（r=0.48，0.46），TNF-α（r=0.55，0.58） and ndotoxin（r=0.67，0.68），and negatively correlated with FEV1（r=-0.54，-0.58），FEV1%pred（r=-0.53，-0.57），and FEV1/FVC（r=-0.56，-0.59）（P<0.05）．The content of bifidobacterium was negatively correlated with C-reactive protein（CRP）（r=-0.22）（P<0.05）．Conclusion　Patients with COPD at stable phase in group C and D of are more likely to have the imbalance of intestinal flora than group A and B，and the intestinal flora status is closely related to the inflammatory indexes and lung function in patients with COPD at stable phase.

Key words: Chronic obstructive pulmonary disease, Intestinal flora, C-reactive protein, Interleukin-6, Interleukin-8, Tumor necrosis factor-alpha, Procalcitonin, Forced vital capacity

摘要： 背景　慢性阻塞性肺疾病（COPD）是一种常见的以持续气流受限为特征的可以预防和治疗的疾病，慢性气道炎症是该病发病机制的关键。人体肠道菌群微生态是维持机体内环境稳定的重要保障因素，可调控炎性递质的释放。目前，关于肠道菌群与COPD之间关系的研究鲜见报道。目的　研究COPD稳定期不同组别患者的肠道菌群状态，并探讨COPD稳定期患者的肠道菌群状态与炎性指标、肺功能的相关性。方法　前瞻性顺序纳入2017年6月—2018年6月在江苏大学附属宜兴医院呼吸内科门诊就诊以及呼吸内科病房收住的符合纳入标准的COPD稳定期患者作为观察组，并按照COPD全球倡议（GOLD）2017综合评估分组标准分为：A、B、C、D 4组，每组患者20例，纳满即止，同期门诊体检健康者20例作为对照组，分析和比较各组肠道菌群状态，并对COPD稳定期患者的肠道菌群状态与炎性指标、肺功能进行相关性分析。结果　C、D组患者的乳酸杆菌、双歧杆菌含量低于对照组、A组和B组，而屎肠球菌、粪肠球菌含量明显高于对照组、A组和B组（P<0.05）。各组患者白介素8（IL-8）、白介素6（IL-6）、肿瘤坏死因子α（TNF-α）、内毒素、第一秒用力呼气末容积（FEV1）、FEV1占预计值的百分比（FEV1%pred）、FEV1/用力肺活量（FEV1/FVC）比较，差异均有统计学意义（P<0.05）。乳酸杆菌、双歧杆菌含量与IL-8（r=-0.50、-0.51）、IL-6（r=-0.57、-0.55）、TNF-α（r=-0.57、-0.56）、降钙素原（PCT）（r=-0.27、-0.24）、内毒素（r=-0.76、-0.76）呈负相关，与FEV1（r=0.44、0.45）、FEV1%pred（r=0.45、0.45）、FEV1/FVC（r=0.51、0.49）呈正相关（P<0.05）；而屎肠球菌、粪肠球菌含量与IL-8（r=0.53、0.55）、IL-6（r=0.48、0.46）、TNF-α（r=0.55、0.58）、内毒素（r=0.67、0.68）呈正相关，与FEV1（r=-0.54、-0.58）、FEV1%pred（r=-0.53、-0.57）、FEV1/FVC（r=-0.56、-0.59）呈负相关（P<0.05）；双歧杆菌与C反应蛋白（CRP）（r=-0.22）呈负相关（P<0.05）。结论　COPD稳定期C、D组患者发生肠道菌群紊乱情况多于A、B组，且COPD稳定期患者的肠道菌群状态与炎性指标及肺功能紧密相关。

关键词: 慢性阻塞性肺疾病；肠道菌群；C反应蛋白；白介素6；白介素8；肿瘤坏死因子&alpha, ；降钙素原；用力肺活量