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Effect of the gut microbiota-derived tryptophan metabolite indole-3-acetic acid in pneumonia

Author

Listed:
  • Robert F. J. Kullberg

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases)

  • Christine C. A. Linge

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases)

  • Bastiaan W. Haak

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases)

  • Prasanjit S. Paul

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases)

  • Joe M. Butler

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases)

  • Nora Wolff

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases)

  • Tjitske S. R. Engelen

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases)

  • Jonne J. Sikkens

    (Amsterdam UMC)

  • Marije K. Bomers

    (Amsterdam UMC)

  • Antoine Lefèvre

    (University of Tours)

  • Olaf L. Cremer

    (Utrecht University)

  • Joris J.T.H. Roelofs

    (University of Amsterdam)

  • Bruno Sovran

    (University of Amsterdam
    University of Amsterdam and Vrije Universiteit Amsterdam
    University of Amsterdam)

  • René Wijngaard

    (University of Amsterdam)

  • Alex F. Vos

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases)

  • Wouter J. Jonge

    (University of Amsterdam
    University Hospital Bonn)

  • Tom Poll

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases
    Amsterdam UMC)

  • W. Joost Wiersinga

    (University of Amsterdam
    Amsterdam institute for Immunology and Infectious diseases
    Amsterdam UMC)

Abstract

Gut microbiota influence the severity of pneumonia by producing metabolites that enhance systemic and pulmonary immune responses. Preclinical studies suggested that gut microbiota-derived indoles have protective effects against numerous diseases, including influenza and abdominal infections. However, the precise role of tryptophan metabolites during pneumonia is unknown. Here, we perform translational analyses in a large general-population cohort (n = 13,464), critically ill patients with severe community-acquired pneumonia (CAP; n = 158; NCT01905033), a randomized human intervention trial on antibiotic-mediated microbiota modulation (NCT03051698), and mice to investigate the effects of tryptophan metabolites, specifically indole-3-acetic acid (IAA), on pneumonia. In the population-based cohort, baseline IAA is associated with a higher risk of future hospital admission for pneumonia (cause-specific hazard ratio 1.15, 95% confidence interval 1.09-1.22 p

Suggested Citation

  • Robert F. J. Kullberg & Christine C. A. Linge & Bastiaan W. Haak & Prasanjit S. Paul & Joe M. Butler & Nora Wolff & Tjitske S. R. Engelen & Jonne J. Sikkens & Marije K. Bomers & Antoine Lefèvre & Olaf, 2025. "Effect of the gut microbiota-derived tryptophan metabolite indole-3-acetic acid in pneumonia," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63611-y
    DOI: 10.1038/s41467-025-63611-y
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