Niu Na, Zhao Jian, Li Haoxiang, Miao Yongen, Chen Futao, Liu Junyong, Cao Limin, Ji Tuo, Gao Feng, Xie Shuanshuan, Zhang Yunfeng
Department of Respiratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, People's Republic of China.
Department of Clinical Laboratory, Tenth People's Hospital of Tongji University, Shanghai, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2025 Jun 17;20:1983-1993. doi: 10.2147/COPD.S511383. eCollection 2025.
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of global mortality and disability. Previous research suggests a relationship between gut microbiota and COPD, yet the causal link remains unclear. Hence, we conducted a dual-sample Mendelian randomization study to elucidate the impact of gut microbiota on COPD.
We utilized single-nucleotide polymorphisms (SNPs) as instrumental variables, and the Inverse Variance Weighted (IVW) method for primary analysis. We explored the causal linkage between gut microbiota species (Coprococcus2, Holdemanella, Allisonella, Anaerostipes, Lachnospiraceae UCG008, Lachnospiraceae UCG010, Prevotella9, Marvinbryantia, Ruminococcaceae UCG013) and COPD through the analysis of genome-wide association study (GWAS) data sourced from a Finnish database. Summary data for COPD (6,915 cases and 186,723 controls), Early onset COPD (3,508 cases and 212,197 controls), admission rate of COPD (9,113 cases and 212,292 controls), related infection of COPD (59,925 cases and 159,867 controls), respiratory dysfunction of COPD (1,031 cases and 186,723 controls), were from FinnGen consortium R7 GWAS.
Our analysis revealed statistically significant correlations between several genera and COPD. Coprococcus2 exhibits a consistent protective role throughout the progression of COPD, evident in both typical COPD [OR=0.750, 95% CI (0.601-0.937)], early-onset cases [OR=0.686, 95% CI (0.511-0.920)], COPD-related hospitalizations [OR=0.724, 95% CI (0.575-0.910)] and infections [OR=0.301, 95% CI (0.094-0.961)]. Holdemanella manifests as a consistent risk factor in the COPD incidence [OR=1.211, 95% CI (1.063-1.380)], early-onset COPD [OR=1.214, 95% CI (1.019-1.446)], COPD hospitalization [OR=1.225, 95% CI (1.072-1.401)] and respiratory impairment (OR:1.645, 95% CI: 1.198-2.258). Allisonella demonstrates protective attributes in COPD occurrence [OR=0.884, 95% CI (0.794-0.984)]. Genera such as Anaerostipes, Lachnospiraceae UCG008, Lachnospiraceae UCG010, and Prevotella9 show protective effects specifically in early-onset COPD. Marvinbryantia and Ruminococcaceae UCG013 are consistently identified as risk factors in onset of typical COPD.
Mendelian randomization studies confirm a causal link between gut microbiota and various COPD types and complications, offering new insights into the disease's pathogenesis, prevention, and treatment.
慢性阻塞性肺疾病（COPD）是全球死亡和残疾的主要原因。先前的研究表明肠道微生物群与COPD之间存在关联，但因果关系仍不明确。因此，我们进行了一项双样本孟德尔随机化研究，以阐明肠道微生物群对COPD的影响。
我们使用单核苷酸多态性（SNP）作为工具变量，并采用逆方差加权（IVW）方法进行初步分析。我们通过分析来自芬兰数据库的全基因组关联研究（GWAS）数据，探索肠道微生物群物种（粪球菌属2、霍尔德曼氏菌属、阿利森氏菌属、厌氧短杆菌属、毛螺菌科UCG008、毛螺菌科UCG010、普雷沃氏菌属9、马文氏菌属、瘤胃球菌科UCG013）与COPD之间的因果联系。COPD（6915例病例和186723例对照）、早发性COPD（3508例病例和212197例对照）、COPD住院率（9113例病例和212292例对照）、COPD相关感染（59925例病例和159867例对照）、COPD呼吸功能障碍（1031例病例和186723例对照）的汇总数据来自芬兰基因组联盟R7 GWAS。
我们的分析揭示了几个属与COPD之间具有统计学意义的相关性。粪球菌属2在COPD的整个病程中都表现出一致的保护作用，在典型COPD [比值比（OR）=0.750，95%置信区间（CI）（0.601 - 0.937）]、早发病例[OR = 0.686，95% CI（0.511 - 0.920）]、COPD相关住院[OR = 0.724，95% CI（0.575 - 0.910）]和感染[OR = 0.301，95% CI（0.094 - 0.961）]中均很明显。霍尔德曼氏菌属在COPD发病[OR = 1.211，95% CI（1.063 - 1.380）]、早发性COPD[OR = 1.214，95% CI（1.019 - 1.446）]、COPD住院[OR = 1.225，95% CI（1.072 - 1.401）]和呼吸功能损害（OR：1.645，95% CI：1.198 - 2.258）中表现为一致的危险因素。阿利森氏菌属在COPD发生中表现出保护特性[OR = 0.884，95% CI（0.794 - 0.984）]。厌氧短杆菌属、毛螺菌科UCG008、毛螺菌科UCG010和普雷沃氏菌属9等属仅在早发性COPD中显示出保护作用。马文氏菌属和瘤胃球菌科UCG013在典型COPD发病中一直被确定为危险因素。
孟德尔随机化研究证实了肠道微生物群与各种COPD类型及并发症之间的因果关系，为该疾病的发病机制、预防和治疗提供了新的见解。
