Daily Sepsis Research Analysis
Analyzed 39 papers and selected 3 impactful papers.
Summary
Three impactful sepsis studies span mechanistic modeling, host–microbiome therapeutics, and ICU pharmacoprevention. A human microvascular 3D model of meningococcal sepsis enables high-resolution, quantitative infection biology; angiotensin-(1-7) restores gut barrier function via microbiome–NLRP6 pathways in murine sepsis; and in septic shock, PPIs reduce upper GI bleeding vs H2RAs without excess infectious harms.
Research Themes
- Advanced human-relevant modeling of meningococcal vascular sepsis
- Renin–angiotensin/MAS axis and microbiome in sepsis gut barrier protection
- Stress ulcer prophylaxis strategy in septic shock (PPI vs H2RA)
Selected Articles
1. An in vitro human vessel model to study
This study introduces a laser photoablation-generated 3D human microvascular model that recapitulates meningococcal vascular colonization. The platform reproduces endothelial integrity and permeability, and enables quantitative, high spatiotemporal readouts of microcolony growth, cytoskeletal remodeling, E-selectin induction, and neutrophil responses, validated against a human-skin xenograft mouse model.
Impact: Provides a human-relevant, quantitative infection platform that bridges 2D culture and animal models, addressing a key bottleneck in sepsis therapeutics discovery. Methodological innovation enables mechanistic dissection of vascular pathogenesis in meningococcemia.
Clinical Implications: While preclinical, the model can accelerate screening of anti-adhesion, anti-colonization, and endothelial-protective therapies for meningococcemia and potentially other septic vasculopathies, and reduce reliance on animal testing.
Key Findings
- Developed a laser photoablation-generated 3D microfluidic human vascular network enabling meningococcal colonization studies.
- Reproduced physiological endothelial integrity and permeability in vitro with quantitative, high spatiotemporal readouts.
- Validated model fidelity by comparing to a human-skin xenograft mouse model, capturing E-selectin induction, cytoskeletal changes, and neutrophil responses.
Methodological Strengths
- Advanced hydrogel engineering with laser photoablation to build physiologic microvasculature.
- Cross-system validation against an in vivo human-skin xenograft model with multiparametric quantitative readouts.
Limitations
- In vitro platform lacks full systemic immune and hemodynamic complexity of sepsis.
- Focused on meningococcal infection; generalizability to other pathogens requires further testing.
Future Directions: Integrate additional immune components (e.g., complement, platelets) and apply the platform to diverse sepsis pathogens and therapeutic screening, including anti-adhesive and endothelial-stabilizing agents.
2. Angiotensin-(1-7) alleviates intestinal barrier dysfunction and dysbiosis in mice with polymicrobial sepsis.
Ang-(1-7) protected the gut barrier and reduced liver injury in CLP-induced sepsis. Its protective effect required the gut microbiota, increased Lactobacillus gasseri abundance, and activated NLRP6 inflammasome to induce antimicrobial peptides in intestinal epithelia. Plasma Ang-(1-7) was decreased in patients with sepsis.
Impact: Identifies a gut–RAS–microbiome axis that restores intestinal homeostasis in sepsis, with mechanistic links through L. gasseri and NLRP6. Offers a plausible therapeutic candidate and microbial targets for barrier protection.
Clinical Implications: Supports evaluating Ang-(1-7) or MAS axis agonism, and microbiome-based strategies (e.g., L. gasseri augmentation) to preserve gut barrier and limit bacterial translocation and secondary organ injury in sepsis.
Key Findings
- Exogenous Ang-(1-7) attenuated intestinal barrier dysfunction and liver damage in CLP-induced sepsis.
- Protective effects depended on the gut microbiota as shown by fecal microbiota transplantation experiments.
- Ang-(1-7) increased Lactobacillus gasseri abundance and activated NLRP6 inflammasome to induce antimicrobial peptides; plasma Ang-(1-7) was decreased in patients with sepsis.
Methodological Strengths
- Use of CLP murine sepsis model with histological and biochemical endpoints across gut and liver.
- Mechanistic dissection with FMT, 16S rDNA profiling, metabolomics, and inflammasome/antimicrobial peptide readouts.
Limitations
- Preclinical murine model; dosing, timing, and safety of Ang-(1-7) require human studies.
- Microbiome analyses were based on 16S rDNA; strain-level functions and causality beyond L. gasseri need further validation.
Future Directions: Translate findings into early-phase clinical trials of Ang-(1-7)/MAS agonists and microbiome interventions; delineate strain-specific mechanisms and optimize delivery strategies.
3. Comparison of Histamine-2 Receptor Antagonists and Proton Pump Inhibitors for Stress Ulcer Prophylaxis in Patients With Septic Shock.
Among 15,102 adults with septic shock, after IPTW adjustment, PPIs were associated with lower UGIB than H2RAs (OR 0.78, 95% CI 0.64–0.96) with consistent findings in a famotidine vs pantoprazole sensitivity analysis. No significant differences were observed in in-hospital mortality, ventilator-associated pneumonia, C. difficile infection, or length of stay.
Impact: Large, nationally representative analysis provides actionable evidence that PPIs reduce UGIB without excess infectious harms in septic shock. This can refine ICU stress ulcer prophylaxis strategies.
Clinical Implications: Prefer PPIs over H2RAs for stress ulcer prophylaxis in septic shock when bleeding risk is high, while continuing infection surveillance; findings support stewardship by avoiding unnecessary therapy changes.
Key Findings
- In IPTW-adjusted analysis, PPIs lowered UGIB compared with H2RAs (OR 0.78; 95% CI, 0.64–0.96).
- No significant differences in in-hospital mortality, ventilator-associated pneumonia, C. difficile infection, or hospital length of stay.
- Sensitivity analysis (famotidine vs pantoprazole) confirmed primary findings (OR 0.80; 95% CI, 0.65–0.97).
Methodological Strengths
- Very large, multicenter cohort with diverse hospitals and propensity weighting (IPTW) to mitigate confounding.
- Drug-specific sensitivity analysis enhances robustness of the primary association.
Limitations
- Retrospective observational design with potential residual confounding and indication bias.
- Exposure misclassification and heterogeneity in dosing/timing or bleeding risk assessment cannot be fully excluded.
Future Directions: Prospective, randomized comparisons in septic shock with standardized bleeding risk stratification and infection surveillance to confirm causality and optimize SUP protocols.