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

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 L. Cremer, Joris J.T.H. Roelofs, Bruno Sovran, René Wijngaard, Alex F. Vos, Wouter J. Jonge, Tom Poll and W. Joost Wiersinga
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Robert F. J. Kullberg: University of Amsterdam
Christine C. A. Linge: University of Amsterdam
Bastiaan W. Haak: University of Amsterdam
Prasanjit S. Paul: University of Amsterdam
Joe M. Butler: University of Amsterdam
Nora Wolff: University of Amsterdam
Tjitske S. R. Engelen: University of Amsterdam
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
René Wijngaard: University of Amsterdam
Alex F. Vos: University of Amsterdam
Wouter J. Jonge: University of Amsterdam
Tom Poll: University of Amsterdam
W. Joost Wiersinga: University of Amsterdam

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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

Date: 2025
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DOI: 10.1038/s41467-025-63611-y

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