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Cited by 12Sepsis Diagnosis and TreatmentGut microbiota and healthClinical Nutrition and Gastroenterology

Sepsis and the diverse organ-gastrointestinal tract axis

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Wang, Jia Dong James, Suan, Enhui, Li, Sean Siwei, Shelat, Vishal G·2025·World Journal of Critical Care Medicine
DOI 10.5492/wjccm.v14.i4.105547PMC PMC12687073
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Abstract

Sepsis remains a leading cause of morbidity and mortality worldwide, driven by a dysregulated host immune response to infection that culminates in multi-organ dysfunction. Recent advances highlight the gut microbiota's pivotal role in modulating immune responses and influencing the pathophysiology of sepsis through the organ-gastrointestinal tract axis. This review synthesizes current evidence on the bidirectional interplay between gut dysbiosis and the dysfunction of major organ systems—liver, lungs, kidneys, brain, and heart—during sepsis. We explore how gut-derived factors such as microbial translocation, endotoxins, and altered metabolite production exacerbate systemic inflammation and organ injury. In particular, we emphasize the roles of short-chain fatty acids, uremic toxins, bile acids, and trimethylamine-N-oxide in mediating immune dysfunction across the gut-organ axes. Therapeutic strategies targeting the gut microbiota— including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation— show promise in preclinical and early clinical settings. However, challenges related to patient heterogeneity, safety, and the lack of precise biomarkers persist. This review consolidates disparate findings to underscore the gut as a central modulator in sepsis and advocates for microbiota-based interventions as adjunctive therapies in sepsis management.

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  • High plasma TMAO is independently associated with increased risk of heart failure, arrhythmias, and 28-day mortality in septic patients.

    “High plasma TMAO is independently associated with increased risk of heart failure, arrhythmias, and 28-day mortality in septic patients (Rastogi et al., 2022; Wang et al., 2025).”

    From Progress on the correlation between sepsis and gut microbiota: a narrative review (2026) · cites this paper as Wang et al., 2025

    The GUT-HEART AXIS section (page unavailable) associates TMAO with adverse cardiovascular outcomes and says elevated levels during sepsis may worsen septic cardiomyopathy. It does not establish an independent association with heart failure, arrhythmias, or 28-day mortality; it discusses arrhythmias and mortality in connection with inflammation and altered cardiac regulation, not TMAO. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Sepsis-associated AKI occurs in up to 50% of septic patients and independently increases mortality.

    “Sepsis-associated AKI occurs in up to 50% of septic patients and independently increases mortality (Wang et al., 2025).”

    From Progress on the correlation between sepsis and gut microbiota: a narrative review (2026) · cites this paper as Wang et al., 2025

    The GUT-KIDNEY AXIS section (page unavailable) discusses sepsis-associated AKI, and SEPSIS PATHOPHYSIOLOGY AND SYSTEMIC IMPACTS (page unavailable) identifies AKI among organ dysfunctions that contribute to sepsis mortality. Neither passage gives an incidence of up to 50% or says AKI independently increases mortality. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Higher indoxyl sulfate levels correlate with more severe AKI and prolonged renal replacement therapy.

    “Higher indoxyl sulfate levels correlate with more severe AKI and prolonged renal replacement therapy (Wang et al., 2025).”

    From Progress on the correlation between sepsis and gut microbiota: a narrative review (2026) · cites this paper as Wang et al., 2025

    The GUT-KIDNEY AXIS section implicates indoxyl sulfate in AKI progression and says these metabolites exacerbate renal injury. It does not report a correlation between measured indoxyl sulfate levels and AKI severity or prolonged renal replacement therapy; searches for those associations found no supporting passage. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Fecal SCFA levels are significantly lower in septic patients who develop AKI than in those without AKI.

    “Fecal SCFA levels are significantly lower in septic patients who develop AKI than in those without AKI (Wang et al., 2025).”

    From Progress on the correlation between sepsis and gut microbiota: a narrative review (2026) · cites this paper as Wang et al., 2025

    The GUT-KIDNEY AXIS section says SCFA production falls during sepsis and links the loss of these metabolites to kidney injury. It does not report fecal SCFA measurements, compare septic patients with and without AKI, or establish a statistically significant difference between those groups. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • In septic mice, gut dysbiosis leads to splenic atrophy, loss of marginal zone B cells, and decreased production of IgM and opsonizing antibodies.

    “In septic mice, gut dysbiosis leads to splenic atrophy, loss of marginal zone B cells, and decreased production of IgM and opsonizing antibodies.”

    From Progress on the correlation between sepsis and gut microbiota: a narrative review (2026) · cites this paper as Wang et al., 2025

    The Sepsis Pathophysiology and Systemic Impacts section links gut dysbiosis to systemic inflammation and immune dysregulation, but does not address splenic atrophy, marginal zone B cells, IgM, or opsonizing antibodies in septic mice. Searches for those terms and for spleen-related findings found no passage supporting the specific claim. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Wang, J. D. J., Suan, E., Li, S. S., & Shelat, V. G.
Affiliations
  • Nanyang Technological University (SG)
  • Tan Tock Seng Hospital (SG)
ORCID
Shelat, Vishal G
Venue
World Journal of Critical Care Medicine
Publisher
Baishideng Publishing Group Inc.
Published
2025-12-09
Volume
14
Issue
4
Pages
105547-105547
ISSN
2220-3141 (ISSN-L)
DOI
10.5492/wjccm.v14.i4.105547
PMC
PMC12687073
OpenAlex
W4416757797
Cited by
12
References
6
Citations by year
2026: 12
FWCI
1.84
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • World Journal of Critical Care Medicine (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
Funders
  • Eli Lilly and Company
  • Edwards Lifesciences
  • Eisai
  • European Society of Intensive Care Medicine
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
Keywords
sepsis, gut microbiota, gut dysbiosis, microbial translocation, endotoxin, short-chain fatty acids, uremic toxins, bile acids, trimethylamine N-oxide, systemic inflammation, multiple organ failure, liver dysfunction, pulmonary dysfunction, renal dysfunction, brain dysfunction, cardiac dysfunction, prebiotics, probiotics, synbiotics, fecal microbiota transplantation, microbiota-based therapy

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