Causal relationship between gut microbiota and pneumonia: a Mendelian randomization and retrospective case-control...

Area of Science:

• Microbiome research
• Gut-lung axis
• Infectious disease epidemiology

Background:

• The gut microbiome's role in the gut-lung axis is recognized, but its causal contribution to pneumonia remains unclear.
• Previous studies explored the gut-lung axis experimentally and epidemiologically.
• This research investigates the potential causal role of gut microbiota in pneumonia development.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota and pneumonia.
• To explore the potential protective effect of specific gut bacteria, like Akkermansia, against pneumonia and its outcomes.
• To provide insights into the gut-lung axis for future research and clinical applications.

Main Methods:

• Utilized gut microbiota genome-wide association studies (GWAS) and pneumonia GWAS data.
• Applied Mendelian randomization (MR) analysis with inverse variance weighting (IVW), weighted median, and MR-Egger methods.
• Employed MR-PRESSO and MR-Egger intercepts to address horizontal pleiotropy.
• Conducted a retrospective case-control study with 16S rRNA sequencing and PERMANOVA analysis on anal swab samples from severe pneumonia patients.

Main Results:

• Identified potential causal links between gut microbiota and pneumonia (critical care) and pneumonia-related 28-day mortality.
• Found a negative correlation between the genus Akkermansia and lactate levels, and reduced ICU days in septic ARDS patients.
• Observed a potential negative causal relationship between Akkermansia and 28-day mortality in critical care pneumonia patients (OR 0.42).

Conclusions:

• Mendelian randomization analysis supports a potential causal relationship between gut microbiota and pneumonia.
• The genus Akkermansia may reduce the risk of 28-day mortality in critical care pneumonia patients.
• Akkermansia may also reduce ICU days and lactate levels in septic ARDS patients, offering insights into the gut-lung axis.