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Causal relationship between gut microbiota and pneumonia: a Mendelian randomization and retrospective case–control study

Peng-Fei Huang, Yan-Qi Liu, Nan Li, Qian-Qian Zhang, Ying-Hao Luo, YuXin Zhang, Yuxin Zhou, Wenjing Mu et al.

BMC Pulmonary Medicine, 2025

2 citations

Abstract

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. 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. 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…

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