AUTHOR=Shang Weifeng , Zhang Sheng , Qian Hang , Huang Sisi , Li Hui , Liu Jiao , Chen Dechang 

TITLE=Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1266230

DOI=10.3389/fimmu.2024.1266230

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>It is unclear what the causal relationship is between the gut microbiota and sepsis. Therefore, we employed Mendelian randomization (MR) to determine whether a causal link exists between the two.</p></sec><sec><title>Methods</title><p>This study used publicly available genome-wide association studies (GWAS) summary data of gut microbiota, sepsis, sepsis (critical care), and sepsis (28-day death in critical care) to perform a two-sample MR analysis. To ensure the robustness of the results, we also conducted a sensitivity analysis.</p></sec><sec><title>Results</title><p>For sepsis susceptibility, inverse variance weighted (IVW) estimates revealed that <italic>Victivallales</italic> (OR = 0.86, 95% CI, 0.78–0.94, <italic>p</italic> = 0.0017) was protective against sepsis, while <italic>Lentisphaerae</italic> (OR = 0.89, 95% CI, 0.80–0.99), <italic>Gammaproteobacteria</italic> (OR = 1.37, 95% CI, 1.08–1.73), <italic>Clostridiaceae1</italic> (OR = 1.21, 95% CI, 1.04–1.40), <italic>RuminococcaceaeUCG011</italic> (OR = 1.10, 95% CI, 1.01–1.20), <italic>Dialister</italic> (OR = 0.85, 95% CI, 0.74–0.97), and <italic>Coprococcus2</italic> (OR = 0.81, 95% CI, 0.69–0.94) presented a suggestive association with the development of sepsis (all <italic>p</italic> &lt; 0.05). For sepsis (critical care), IVW estimates indicated that <italic>Lentisphaerae</italic> (OR = 0.70, 95% CI, 0.53–0.93), <italic>Victivallales</italic> (OR = 0.67, 95% CI, 0.50–0.91), <italic>Anaerostipes</italic> (OR = 0.49, 95% CI, 0.31–0.76), <italic>LachnospiraceaeUCG004</italic> (OR = 0.51, 95% CI, 0.34–0.77), and <italic>Coprococcus1</italic> (OR = 0.66, 95% CI, 0.44–0.99) showed a suggestive negative correlation with sepsis (critical care) (all <italic>p</italic> &lt; 0.05). For sepsis (28-day death in critical care), IVW estimates suggested that four bacterial taxa had a normally significant negative correlation with the risk of sepsis-related death, including <italic>Victivallales</italic> (OR = 0.54, 95% CI, 0.30–0.95), <italic>Coprococcus2</italic> (OR = 0.34, 95% CI, 0.14–0.83), <italic>Ruminiclostridium6</italic> (OR = 0.43, 95% CI, 0.22–0.83), and <italic>Coprococcus1</italic> (OR = 0.45, 95% CI, 0.21–0.97), while two bacterial taxa were normally significantly positively linked to the risk of sepsis-related death, namely, <italic>Mollicutes</italic> (OR = 2.03, 95% CI, 1.01–4.08) and <italic>Bacteroidales</italic> (OR = 2.65, 95% CI, 1.18–5.96) (all <italic>p</italic> &lt; 0.05). The robustness of the above correlations was verified by additional sensitivity analyses.</p></sec><sec><title>Conclusion</title><p>This MR research found that several gut microbiota taxa were causally linked to the risk of sepsis, sepsis in critical care, and sepsis-related 28-day mortality in critical care.</p></sec>