{"title":"肠道菌群与肺炎的因果关系:孟德尔随机和回顾性病例对照研究。","authors":"Pengfei Huang, Yanqi Liu, Nana Li, Qianqian Zhang, Yinghao Luo, Yuxin Zhang, Yuxin Zhou, Wenjing Mu, Mengyao Yuan, Yuhan Liu, Yu Xin, Hongxu Li, Yahui Peng, Xibo Wang, Mingyan Zhao, Kaijiang Yu, Changsong Wang","doi":"10.1186/s12890-025-03899-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The relationship between microbiota and the gut-lung axis has been extensively studied in both experimental and epidemiological contexts. However, it is still unclear whether the gut microbiome plays a causal role in the development of pneumonia.</p><p><strong>Methods: </strong>Our study initially identified the genetic instruments in the gut microbiota GWAS across phylum, class, order, family, and genus levels. Pneumonia data were sourced from the open GWAS project of the Integrated Epidemiology Group (IEU). Mendelian randomization (MR) analysis employed several methods such as inverse variance weighting (IVW), weighted median, and MR-Egger, with Cochran's Q were calculated to assess heterogeneity via IVW and MR-Egger. Additionally, MR-PRESSO and MR-Egger intercepts were utilized to mitigate horizontal pleiotropy. A retrospective case-control study collected anal swab samples from severe pneumonia patients on the 1st and 3rd days after ICU admission. Samples were analyzed using 16S ribosomal ribonucleic acid (16S rRNA) and PERMANOVA analysis.</p><p><strong>Results: </strong>Eleven potential causal relationships between the gut microbiome and pneumonia (critical care), as well as nine potential causal relationships between the gut microbiome and pneumonia (28-day death in critical care) were identified. By integrating the results of PERMANOVA analysis with Mendelian randomization analysis, we were able to determine a negative correlation between genus Akkermansia and lactate levels, as well as length of ICU days in patients with septic acute respiratory distress syndrome (ARDS). Moreover, we found a potential negative causal relationship between the genus Akkermansia and pneumonia (28-day death in critical care) (OR 0.42, 95% CI 0.22-0.79, P = 0.007).</p><p><strong>Conclusions: </strong>Our Mendelian randomization analysis has provided evidence for a potential causal relationship between gut microbiota and pneumonia. Furthermore, we observed that the genus Akkermansia may decrease the risk of pneumonia (28-day death in critical care), as observed in septic ARDS patients which Akkermansia could reduce ICU days and lactate levels. These findings provide valuable insights into the gut-lung axis and have the latent to inform future research in this field.</p><p><strong>Trial registration: </strong>The study was registered at the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/index.html , ChiCTR2300075450).</p>","PeriodicalId":9148,"journal":{"name":"BMC Pulmonary Medicine","volume":"25 1","pages":"449"},"PeriodicalIF":2.8000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Causal relationship between gut microbiota and pneumonia: a Mendelian randomization and retrospective case-control study.\",\"authors\":\"Pengfei Huang, Yanqi Liu, Nana Li, Qianqian Zhang, Yinghao Luo, Yuxin Zhang, Yuxin Zhou, Wenjing Mu, Mengyao Yuan, Yuhan Liu, Yu Xin, Hongxu Li, Yahui Peng, Xibo Wang, Mingyan Zhao, Kaijiang Yu, Changsong Wang\",\"doi\":\"10.1186/s12890-025-03899-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The relationship between microbiota and the gut-lung axis has been extensively studied in both experimental and epidemiological contexts. However, it is still unclear whether the gut microbiome plays a causal role in the development of pneumonia.</p><p><strong>Methods: </strong>Our study initially identified the genetic instruments in the gut microbiota GWAS across phylum, class, order, family, and genus levels. Pneumonia data were sourced from the open GWAS project of the Integrated Epidemiology Group (IEU). Mendelian randomization (MR) analysis employed several methods such as inverse variance weighting (IVW), weighted median, and MR-Egger, with Cochran's Q were calculated to assess heterogeneity via IVW and MR-Egger. Additionally, MR-PRESSO and MR-Egger intercepts were utilized to mitigate horizontal pleiotropy. A retrospective case-control study collected anal swab samples from severe pneumonia patients on the 1st and 3rd days after ICU admission. Samples were analyzed using 16S ribosomal ribonucleic acid (16S rRNA) and PERMANOVA analysis.</p><p><strong>Results: </strong>Eleven potential causal relationships between the gut microbiome and pneumonia (critical care), as well as nine potential causal relationships between the gut microbiome and pneumonia (28-day death in critical care) were identified. By integrating the results of PERMANOVA analysis with Mendelian randomization analysis, we were able to determine a negative correlation between genus Akkermansia and lactate levels, as well as length of ICU days in patients with septic acute respiratory distress syndrome (ARDS). Moreover, we found a potential negative causal relationship between the genus Akkermansia and pneumonia (28-day death in critical care) (OR 0.42, 95% CI 0.22-0.79, P = 0.007).</p><p><strong>Conclusions: </strong>Our Mendelian randomization analysis has provided evidence for a potential causal relationship between gut microbiota and pneumonia. 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引用次数: 0
摘要
背景:微生物群与肠-肺轴之间的关系在实验和流行病学背景下都得到了广泛的研究。然而,目前尚不清楚肠道微生物群是否在肺炎的发展中起因果作用。方法:我们的研究初步确定了跨门、纲、目、科和属水平的肠道微生物群GWAS的遗传工具。肺炎数据来自综合流行病学小组(IEU)的开放GWAS项目。孟德尔随机化(MR)分析采用逆方差加权(IVW)、加权中位数和MR- egger等方法,并计算Cochran’s Q,通过IVW和MR- egger评估异质性。此外,利用MR-PRESSO和MR-Egger截距来减轻水平多效性。回顾性病例对照研究收集重症肺炎患者在ICU入院后第1天和第3天的肛门拭子样本。采用16S核糖体核糖核酸(16S rRNA)和PERMANOVA分析对样品进行分析。结果:确定了肠道微生物群与肺炎(重症监护)之间的11种潜在因果关系,以及肠道微生物群与肺炎(重症监护28天死亡)之间的9种潜在因果关系。通过整合PERMANOVA分析和孟德尔随机化分析的结果,我们能够确定Akkermansia属与脓毒性急性呼吸窘迫综合征(ARDS)患者的乳酸水平以及ICU天数之间存在负相关。此外,我们发现Akkermansia属与肺炎(重症监护28天死亡)之间存在潜在的负相关关系(OR 0.42, 95% CI 0.22-0.79, P = 0.007)。结论:我们的孟德尔随机分析为肠道菌群和肺炎之间潜在的因果关系提供了证据。此外,我们观察到Akkermansia属可能降低肺炎(重症监护28天死亡)的风险,正如在脓毒性ARDS患者中观察到的那样,Akkermansia属可以减少ICU天数和乳酸水平。这些发现为肠-肺轴提供了有价值的见解,并有可能为该领域的未来研究提供信息。试验注册:本研究已在中国临床试验注册中心注册(https://www.chictr.org.cn/index.html, ChiCTR2300075450)。
Causal relationship between gut microbiota and pneumonia: a Mendelian randomization and retrospective case-control study.
Background: The relationship between microbiota and the gut-lung axis has been extensively studied in both experimental and epidemiological contexts. However, it is still unclear whether the gut microbiome plays a causal role in the development of pneumonia.
Methods: Our study initially identified the genetic instruments in the gut microbiota GWAS across phylum, class, order, family, and genus levels. Pneumonia data were sourced from the open GWAS project of the Integrated Epidemiology Group (IEU). Mendelian randomization (MR) analysis employed several methods such as inverse variance weighting (IVW), weighted median, and MR-Egger, with Cochran's Q were calculated to assess heterogeneity via IVW and MR-Egger. Additionally, MR-PRESSO and MR-Egger intercepts were utilized to mitigate horizontal pleiotropy. A retrospective case-control study collected anal swab samples from severe pneumonia patients on the 1st and 3rd days after ICU admission. Samples were analyzed using 16S ribosomal ribonucleic acid (16S rRNA) and PERMANOVA analysis.
Results: Eleven potential causal relationships between the gut microbiome and pneumonia (critical care), as well as nine potential causal relationships between the gut microbiome and pneumonia (28-day death in critical care) were identified. By integrating the results of PERMANOVA analysis with Mendelian randomization analysis, we were able to determine a negative correlation between genus Akkermansia and lactate levels, as well as length of ICU days in patients with septic acute respiratory distress syndrome (ARDS). Moreover, we found a potential negative causal relationship between the genus Akkermansia and pneumonia (28-day death in critical care) (OR 0.42, 95% CI 0.22-0.79, P = 0.007).
Conclusions: Our Mendelian randomization analysis has provided evidence for a potential causal relationship between gut microbiota and pneumonia. Furthermore, we observed that the genus Akkermansia may decrease the risk of pneumonia (28-day death in critical care), as observed in septic ARDS patients which Akkermansia could reduce ICU days and lactate levels. These findings provide valuable insights into the gut-lung axis and have the latent to inform future research in this field.
Trial registration: The study was registered at the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/index.html , ChiCTR2300075450).
期刊介绍:
BMC Pulmonary Medicine is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of pulmonary and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.