ArticleBMC pulmonary medicine2025
Causal relationship between gut microbiota and pneumonia: a Mendelian randomization and retrospective case-control study.
Article in BMC pulmonary medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Differential regulatory mechanisms of gut-derived SCFAs (acetate, propionate, butyrate) on the pulmonary TLR2 signaling pathway and their roles in the inflammatory balance of bacterial pneumonia.European journal of medical research · 2026Review
- Gut microbiota-regulated cell death: a review on pyroptosis, ferroptosis, and related mechanisms.Frontiers in microbiology · 2026Review
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17 authors.
Funding
Abstract
backgroundThe 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.
methodsOur 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.
resultsEleven 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).
conclusionsOur 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 registrationThe study was registered at the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/index.html , ChiCTR2300075450).
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