Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 31:15:1266230.
doi: 10.3389/fimmu.2024.1266230. eCollection 2024.

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

Weifeng Shang #  1 , Sheng Zhang #  1 , Hang Qian #  1 , Sisi Huang  1 , Hui Li  1 , Jiao Liu  1 , Dechang Chen  1
Affiliations

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

Weifeng Shang et al. Front Immunol. .

Abstract

Background: 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.

Methods: 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.

Results: For sepsis susceptibility, inverse variance weighted (IVW) estimates revealed that Victivallales (OR = 0.86, 95% CI, 0.78-0.94, p = 0.0017) was protective against sepsis, while Lentisphaerae (OR = 0.89, 95% CI, 0.80-0.99), Gammaproteobacteria (OR = 1.37, 95% CI, 1.08-1.73), Clostridiaceae1 (OR = 1.21, 95% CI, 1.04-1.40), RuminococcaceaeUCG011 (OR = 1.10, 95% CI, 1.01-1.20), Dialister (OR = 0.85, 95% CI, 0.74-0.97), and Coprococcus2 (OR = 0.81, 95% CI, 0.69-0.94) presented a suggestive association with the development of sepsis (all p < 0.05). For sepsis (critical care), IVW estimates indicated that Lentisphaerae (OR = 0.70, 95% CI, 0.53-0.93), Victivallales (OR = 0.67, 95% CI, 0.50-0.91), Anaerostipes (OR = 0.49, 95% CI, 0.31-0.76), LachnospiraceaeUCG004 (OR = 0.51, 95% CI, 0.34-0.77), and Coprococcus1 (OR = 0.66, 95% CI, 0.44-0.99) showed a suggestive negative correlation with sepsis (critical care) (all p < 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 Victivallales (OR = 0.54, 95% CI, 0.30-0.95), Coprococcus2 (OR = 0.34, 95% CI, 0.14-0.83), Ruminiclostridium6 (OR = 0.43, 95% CI, 0.22-0.83), and Coprococcus1 (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, Mollicutes (OR = 2.03, 95% CI, 1.01-4.08) and Bacteroidales (OR = 2.65, 95% CI, 1.18-5.96) (all p < 0.05). The robustness of the above correlations was verified by additional sensitivity analyses.

Conclusion: 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.

Keywords: Mendelian randomization; causality; gut microbiota; sepsis; sepsis-related death.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The analysis process of our research. GWAS, genome-wide association study; MR, Mendelian randomization; SNPs, single-nucleotide polymorphisms; IVW, inverse variance weighted; WM, weighted median; MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier.
Figure 2
Figure 2
Causal analysis of gut microbiota and sepsis. (A) All results of IVW between gut microbiota and sepsis. (B) IVW results of gut microbiota taxa with causality to sepsis.
Figure 3
Figure 3
Investigating the causal relationship between gut microbiota and sepsis requiring critical care. (A) All results of IVW between gut microbiota and sepsis requiring critical care. (B) IVW results of gut microbiota taxa with causality to sepsis requiring critical care.
Figure 4
Figure 4
Causal analysis of gut microbiota and sepsis-related 28-day mortality in critical care. (A) All results of IVW between gut microbiota and sepsis-related 28-day mortality in critical care. (B) IVW results of gut microbiota taxa with causality to sepsis-related 28-day mortality in critical care.
Figure 5
Figure 5
The causality between gut microbiota and sepsis, sepsis requiring critical care, and sepsis-related 28-day mortality in critical care by Mendelian randomization analysis. The thickness of the line represents the p-value.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. . Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med (2021) 47:1181–247. doi: 10.1007/s00134-021-06506-y - DOI - PMC - PubMed
    1. Minasyan H. Sepsis: mechanisms of bacterial injury to the patient. Scand J Trauma Resusc Emerg Med (2019) 27:19. doi: 10.1186/s13049-019-0596-4 - DOI - PMC - PubMed
    1. Costa SP, Carvalho CM. Burden of bacterial bloodstream infections and recent advances for diagnosis. Pathog Dis (2022) 80:ftac027. doi: 10.1093/femspd/ftac027 - DOI - PubMed
    1. Lange K, Buerger M, Stallmach A, Bruns T. Effects of antibiotics on gut microbiota. Dig Dis (2016) 34:260–8. doi: 10.1159/000443360 - DOI - PubMed
    1. Liu Z, Li N, Fang H, Chen X, Guo Y, Gong S, et al. . Enteric dysbiosis is associated with sepsis in patients. FASEB J (2019) 33:12299–310. doi: 10.1096/fj.201900398RR - DOI - PMC - PubMed

Publication types