Table_1_Genetic association and bidirectional Mendelian randomization for causality between gut microbiota and six lung diseases.XLSX

PurposesIncreasing evidence suggests that intestinal microbiota correlates with the pathological processes of many lung diseases. This study aimed to investigate the causality of gut microbiota and lung diseases.MethodsGenetic information on intestinal flora and lung diseases [asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), lower respiratory tract infection (LRTI), pulmonary arterial hypertension (PAH)] and lung function was obtained from UK Biobank, FinnGen, and additional studies. A Mendelian randomization (MR) analysis was conducted to explore the causal association between gut microbiota and lung diseases.ResultsThe genetic liability to lung diseases may be associated with the abundance of certain microbiota taxa. Specifically, the genus Prevotella (p = 0.041) was related to a higher risk of asthma; the family Defluviitaleaceae (p = 0.002) and its child taxon were identified as a risk factor for chronic bronchitis; the abundance of the genus Prevotella (p = 0.020) was related to a higher risk of ILD; the family Coriobacteriaceae (p = 0.011) was identified to have a positive effect on the risk of LRTI; the genus Lactobacillus (p = 0.0297) has been identified to be associated with an increased risk of PAH, whereas the genus Holdemanella (p = 0.0154) presented a causal decrease in COPD risk; the order Selenomonadales was identified to have a positive effect on the risk of FEV1(p = 0.011). The reverse TSMR analysis also provided genetic evidence of reverse causality from lung diseases to the gut microbiota.ConclusionThis data-driven MR analysis revealed that gut microbiota was causally associated with lung diseases, providing genetic evidence for further mechanistic and clinical studies to understand the crosstalk between gut microbiota and lung diseases.

日益增多的证据表明，肠道微生物群与多种肺部疾病的病理过程相关联。本研究旨在探讨肠道微生物群与肺部疾病之间的因果关系。研究方法：从英国生物样本库、FinnGen以及额外的研究中获取了关于肠道菌群和肺部疾病[哮喘、慢性支气管炎、慢性阻塞性肺疾病 (COPD)、间质性肺疾病 (ILD)、下呼吸道感染 (LRTI)、肺动脉高压 (PAH)]以及肺功能遗传信息。通过孟德尔随机化 (MR) 分析，探究了肠道微生物群与肺部疾病之间的因果关系。研究结果：肺部疾病的遗传易感性可能与某些微生物类群丰度有关。具体而言，普雷沃氏菌属（p = 0.041）与哮喘的高风险相关；Defluviitaleaceae科（p = 0.002）及其子类群被认定为慢性支气管炎的风险因素；普雷沃氏菌属的丰度（p = 0.020）与ILD的高风险相关；Coriobacteriaceae科（p = 0.011）被发现对LRTI风险有积极影响；乳酸杆菌属（p = 0.0297）已被确认为与肺动脉高压增加的风险相关，而Holdemanella属（p = 0.0154）则表现出降低COPD风险的因果效应；Selenomonadales目被发现对FEV1风险有积极影响。反向TSMR分析也提供了从肺部疾病到肠道微生物群的逆向因果关系的遗传证据。结论：基于数据的MR分析揭示了肠道微生物群与肺部疾病之间的因果关系，为深入探讨肠道微生物群与肺部疾病之间的相互作用提供了遗传证据，并为后续的机制和临床研究提供了基础。