Microbial metabolite oxindole curbs acute lung injury by suppressing CXCL13 - PubMed
3 hours ago
- #gut-lung axis
- #microbial metabolites
- #acute lung injury
- The gut-lung axis plays a role in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), but its mechanisms are not well understood.
- Untargeted metabolomics showed dysregulation of tryptophan metabolism in ARDS patients compared to healthy controls.
- High dietary tryptophan intake alleviated ALI severity in mice, while deficiency worsened it, with protection being gut microbiota-dependent.
- Lactobacillus johnsonii (L. johnsonii) was found to be depleted during ALI, and its supplementation attenuated ALI, but only with sufficient dietary tryptophan.
- L. johnsonii converts tryptophan into oxindole, which suppresses CXCL13 in pulmonary macrophages via the aryl hydrocarbon receptor-RelA pathway.
- Both genetic and pharmacological inhibition of CXCL13 improved ALI symptoms.
- Oxindole and CXCL13 levels correlated with ARDS severity in patients, indicating clinical relevance.
- The study highlights a microbiota-dependent gut-lung axis mediated by dietary tryptophan-derived oxindole, suggesting potential therapeutic targets.