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The bug, the burden, and the biology: beyond host-centric phenotyping in sepsis

Georgios D Kitsios1,2, Rebecca M Baron3

  • 1Division of Pulmonary, Allergy, Critical Care and Sleep Medicine and.

The Journal of Clinical Investigation
|March 16, 2026
PubMed

Insights

Pathogen characteristics, like E. coli, independently influence sepsis subphenotypes, impacting treatment effectiveness. Understanding the interplay between host and pathogen is crucial for precision critical care medicine.

Area of Science:

  • Critical care medicine
  • Infectious diseases
  • Immunology

Background:

  • Sepsis subtyping traditionally focuses on host responses (hyperinflammatory vs. hypoinflammatory).
  • Previous models overlooked the independent contribution of infectious agents to sepsis phenotypes.

Purpose of the Study:

  • To investigate the independent role of pathogen characteristics in determining sepsis subphenotypes.
  • To explore how pathogen-host interactions influence clinical outcomes and treatment efficacy.

Main Methods:

  • Analysis of host biomarkers and clinical data alongside pathogen identification.
  • Utilized animal models to establish causality.
  • Reanalyzed observational cohort and clinical trial data.

Main Results:

  • Enterobacterales infections, especially E. coli, are linked to hyperinflammatory sepsis subphenotypes, irrespective of illness severity.
  • Bacterial burden, barrier breach, and pathogen-associated molecular patterns affect sepsis classification.
  • Lactate clearance and polymyxin B hemoadsorption efficacy vary based on sepsis subphenotype and pathogen.

Conclusions:

  • Pathogen factors significantly contribute to sepsis subphenotypes, challenging the host-centric view.
  • Integrative host-pathogen phenotyping is essential for advancing precision medicine in critical illness.
  • Tailoring treatments based on both host and pathogen profiles can improve patient outcomes.

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