Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation
Open accessAbstract
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.
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Challenges include high inter-individual variability, lack of standardized timing/strain/dosing, no consensus on an "ideal microbiota," and potential risks - especially in immunocompromised patients.
“Challenges include high inter-individual variability, lack of standardized timing/strain/dosing, no consensus on an “ideal microbiota,” and potential risks – especially in immunocompromised patients (Han et al., 2024; Shang et al., 2024).”
From Progress on the correlation between sepsis and gut microbiota: a narrative review (2026) · cites this paper as Shang et al., 2024
The Discussion (page not specified) says gut microbiota is influenced by diet, lifestyle, and medication, which lends limited support to variability as a challenge. It does not establish high inter-individual variability or discuss standardized timing, strains, or dosing, an “ideal microbiota,” or risks for immunocompromised patients. Its stated limitations concern the genetic analysis rather than those intervention challenges. (LLM, conf=0.79)
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“Challenges include high inter-individual variability, lack of standardized timing/strain/dosing, no consensus on an “ideal microbiota,” and potential risks – especially in immunocompromised patients (Han et al., 2024; Shang et al., 2024).”
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- Authors
- Shang, W., Zhang, S., Qian, H., Huang, S., Li, H., Liu, J., & Chen, D.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Liu, Jiao
- Chen, Dechang
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2024-01-31
- Volume
- 15
- Pages
- 1266230-1266230
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC10867964
- OpenAlex
- W4391397023
- Cited by
- 23
- References
- 49
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 6
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82172152, 82241044)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Keywords
- gut microbiota, sepsis, sepsis mortality, causal inference, Lentisphaerae, Gammaproteobacteria, Clostridiaceae, Ruminococcaceae, Dialister, Coprococcus, Anaerostipes, Lachnospiraceae, intensive care, host-microbe interactions
- MeSH terms
- Gastrointestinal Microbiome, Humans, Sepsis, Bacteroidetes, Genome-Wide Association Study, Mendelian Randomization Analysis
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