肠道微生物群与慢性阻塞性肺疾病的因果关系：一项双向两样本孟德尔随机化研究。
Causal Relationship Between Gut Microbiota and Chronic Obstructive Pulmonary Disease: A Bidirectional Two-Sample Mendelian Randomization Study.
机构信息
Department of Pulmonary and Critical Care Medicine, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People's Republic of China.
Department of Orthopedics and Traumatology, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People's Republic of China.
出版信息
Int J Chron Obstruct Pulmon Dis. 2024 Sep 2;19:1957-1969. doi: 10.2147/COPD.S464917. eCollection 2024.
BACKGROUND
The associations between gut microbiota and chronic obstructive pulmonary disease (COPD) have gained increasing attention and research interest among scholars. However, it remains unclear whether gut microbiota serves as a causal factor for COPD or if it is a consequence of the disease. Therefore, we investigated the causal relationship between COPD and gut microbiota, with intention of providing novel insights and references for clinical diagnosis and treatment.
METHODS
Based on the genome-wide association study (GWAS) data, we employed MR-Egger regression, random-effects inverse variance-weighted (IVW) method, and weighted median method for bidirectional Mendelian randomization (MR) analysis. We conducted Cochran's Q test for heterogeneity assessment and performed multivariable analysis, sensitivity analysis, and heterogeneity testing to validate the reliability and stability of results.
RESULTS
Utilizing MR analysis, mainly employing the IVW method, we detected a collective of 11 gut microbiota species that exhibited associations with COPD. Among them, Bacteroidia, family XIII, Clostridium innocuum group, Barnesiella, Collinsella, Lachnospiraceae NK4A136 group, Lachnospiraceae UCG004, Lachnospiraceae UCG010, and Bacteroidales were found to be protective factors for COPD. On the other hand, Holdemanella and Marvinbryantia were identified as risk factors for COPD. Individuals with elevated levels of Holdemanella exhibited a 1.141-fold higher risk of developing COPD compared to their healthy counterparts, and those with increased levels of Marvinbryantia had a 1.154-fold higher risk. Reverse MR analysis yielded no evidence indicating a causal relationship between gut microbiota and COPD occurrence.
CONCLUSION
Our study established a causal link between 11 specific gut microbiota species and COPD, offering novel insights and valuable references for targeted therapies in the clinical management of COPD. However, our results were mainly based on the analysis of database, and further clinical studies are needed to clarify the effects of gut microbiota on COPD and its specific protective mechanism.
背景
肠道微生物群与慢性阻塞性肺疾病（COPD）之间的关联引起了学者们越来越多的关注和研究兴趣。然而，肠道微生物群是否是 COPD 的因果因素，还是疾病的结果，目前仍不清楚。因此，我们研究了 COPD 和肠道微生物群之间的因果关系，旨在为 COPD 的临床诊断和治疗提供新的见解和参考。
方法
基于全基因组关联研究（GWAS）数据，我们采用 MR-Egger 回归、随机效应逆方差加权（IVW）方法和加权中位数法进行双向 Mendelian 随机化（MR）分析。我们进行 Cochran's Q 检验评估异质性，并进行多变量分析、敏感性分析和异质性检验，以验证结果的可靠性和稳定性。
结果
利用 MR 分析，主要采用 IVW 方法，我们检测到 11 种肠道微生物群与 COPD 相关。其中，拟杆菌门、XIII 科、无丙二酸密螺旋体群、Barnesiella、Collinsella、Lachnospiraceae NK4A136 群、Lachnospiraceae UCG004、Lachnospiraceae UCG010 和拟杆菌目是 COPD 的保护因素。另一方面，豪氏菌属和 Marvinbryantia 被认为是 COPD 的危险因素。与健康对照组相比，豪氏菌属水平升高的个体患 COPD 的风险增加了 1.141 倍，而 Marvinbryantia 水平升高的个体患 COPD 的风险增加了 1.154 倍。反向 MR 分析没有证据表明肠道微生物群与 COPD 发生之间存在因果关系。
结论
我们的研究确立了 11 种特定肠道微生物群与 COPD 之间的因果关系，为 COPD 的临床管理中的靶向治疗提供了新的见解和有价值的参考。然而，我们的结果主要基于数据库的分析，需要进一步的临床研究来阐明肠道微生物群对 COPD 的影响及其特定的保护机制。
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