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Short-Chain Fatty Acids: A Key Modulator of Sepsis-Associated Acute Respiratory Distress Syndrome

Yuting Sun1,2, Meilin He3, Jiaqi Li1

  • 1Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Department of Emergency, Shanghai, 200062, People's Republic of China.

Journal of Inflammation Research
|June 25, 2026
PubMed

Insights

Intestinal flora imbalance contributes to sepsis-associated acute respiratory distress syndrome (ARDS). Short-chain fatty acids (SCFAs) play a bidirectional role, offering potential for targeted therapies.

Area of Science:

  • Microbiology
  • Immunology
  • Pulmonology

Background:

  • Sepsis-associated acute respiratory distress syndrome (ARDS) is a fatal complication.
  • Intestinal flora imbalance is a key factor in ARDS pathogenesis.
  • Microbial translocation, inflammation, and immune dysregulation link gut dysbiosis to lung injury.

Purpose of the Study:

  • To review the mechanisms of ARDS caused by intestinal flora imbalance.
  • To explore the bidirectional regulatory properties of short-chain fatty acids (SCFAs).
  • To discuss intestinal flora-based intervention strategies for sepsis-associated ARDS.

Main Methods:

  • Systematic review of existing literature.
  • Analysis of the role of SCFAs (acetate, propionate, butyrate) in ARDS.
  • Examination of SCFA mechanisms involving histone deacetylase (HDACs) and G protein-coupled receptors (GPCRs).

Main Results:

  • Intestinal dysbiosis promotes ARDS through microbial translocation, systemic inflammation, and immune dysregulation.
  • Depletion of SCFAs accelerates ARDS progression.
  • SCFAs exert protective effects via anti-inflammatory, immunomodulatory, and barrier-protective actions.
  • SCFAs exhibit concentration, type, and inflammation stage-dependent bidirectional regulatory properties.

Conclusions:

  • Understanding the bidirectional regulation of SCFAs is crucial for personalized ARDS therapies.
  • Targeting intestinal flora and SCFA metabolism offers novel therapeutic avenues for sepsis-associated ARDS.
  • Precision dosing and personalized interventions are key for effective clinical management.
Keywords:
SCFAsgut microbiotagut-lung axisimmunomodulationsepsis-associated ARDS

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