AUTHOR=Gao Yuzheng , Liu Lidan , Cui Yuning , Zhang Jiaxin , Wu Xiuying 

TITLE=The causality of gut microbiota on onset and progression of sepsis: a bi-directional Mendelian randomization analysis

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1266579

DOI=10.3389/fimmu.2024.1266579

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Several observational studies have proposed a potential link between gut microbiota and the onset and progression of sepsis. Nevertheless, the causality of gut microbiota and sepsis remains debatable and warrants more comprehensive exploration.</p></sec><sec><title>Methods</title><p>We conducted a two-sample Mendelian randomization (MR) analysis to test the causality between gut microbiota and the onset and progression of sepsis. The genome-wide association study (GWAS) summary statistics for 196 bacterial traits were extracted from the MiBioGen consortium, whereas the GWAS summary statistics for sepsis and sepsis-related outcomes came from the UK Biobank. The inverse-variance weighted (IVW) approach was the primary method used to examine the causal association. To complement the IVW method, we utilized four additional MR methods. We performed a series of sensitivity analyses to examine the robustness of the causal estimates.</p></sec><sec><title>Results</title><p>We assessed the causality of 196 bacterial traits on sepsis and sepsis-related outcomes. Genus <italic>Coprococcus2</italic> [odds ratio (OR) 0.81, 95% confidence interval (CI) (0.69–0.94), <italic>p</italic> = 0.007] and genus <italic>Dialister</italic> (OR 0.85, 95% CI 0.74–0.97, <italic>p</italic> = 0.016) had a protective effect on sepsis, whereas genus <italic>Ruminococcaceae UCG011</italic> (OR 1.10, 95% CI 1.01–1.20, <italic>p</italic> = 0.024) increased the risk of sepsis. When it came to sepsis requiring critical care, genus <italic>Anaerostipes</italic> (OR 0.49, 95% CI 0.31–0.76, <italic>p</italic> = 0.002), genus <italic>Coprococcus1</italic> (OR 0.65, 95% CI 0.43–1.00, <italic>p</italic> = 0.049), and genus <italic>Lachnospiraceae UCG004</italic> (OR 0.51, 95% CI 0.34–0.77, <italic>p</italic> = 0.001) emerged as protective factors. Concerning 28-day mortality of sepsis, genus <italic>Coprococcus1</italic> (OR 0.67, 95% CI 0.48–0.94, <italic>p</italic> = 0.020), genus <italic>Coprococcus2</italic> (OR 0.48, 95% CI 0.27–0.86, <italic>p</italic> = 0.013), genus <italic>Lachnospiraceae FCS020</italic> (OR 0.70, 95% CI 0.52–0.95, <italic>p</italic> = 0.023), and genus <italic>Victivallis</italic> (OR 0.82, 95% CI 0.68–0.99, <italic>p</italic> = 0.042) presented a protective effect, whereas genus <italic>Ruminococcus torques group</italic> (OR 1.53, 95% CI 1.00–2.35, <italic>p</italic> = 0.049), genus <italic>Sellimonas</italic> (OR 1.25, 95% CI 1.04–1.50, <italic>p</italic> = 0.019), and genus <italic>Terrisporobacter</italic> (OR 1.43, 95% CI 1.02–2.02, <italic>p</italic> = 0.040) presented a harmful effect. Furthermore, genus <italic>Coprococcus1</italic> (OR 0.42, 95% CI 0.19–0.92, <italic>p</italic> = 0.031), genus <italic>Coprococcus2</italic> (OR 0.34, 95% CI 0.14–0.83, <italic>p</italic> = 0.018), and genus <italic>Ruminiclostridium6</italic> (OR 0.43, 95% CI 0.22–0.83, <italic>p</italic> = 0.012) were associated with a lower 28-day mortality of sepsis requiring critical care.</p></sec><sec><title>Conclusion</title><p>This MR analysis unveiled a causality between the 21 bacterial traits and sepsis and sepsis-related outcomes. Our findings may help the development of novel microbiota-based therapeutics to decrease the morbidity and mortality of sepsis.</p></sec>