Bridging of host-microbiota tryptophan partitioning by the serotonin pathway in fungal pneumonia.
Giorgia RengaFiorella D'OnofrioMarilena ParianoRoberta GalariniCarolina BarolaClaudia StincardiniMarina M BelletHelmut EllemunterCornelia Lass-FlörlClaudio CostantiniValerio NapolioniAllison K EhrlichCinzia AntognelliMassimo FiniEnrico GaraciEmilia NunziLuigina RomaniPublished in: Nature communications (2023)
The aromatic amino acid L-tryptophan (Trp) is essentially metabolized along the host and microbial pathways. While much is known about the role played by downstream metabolites of each pathways in intestinal homeostasis, their role in lung immune homeostasis is underappreciated. Here we have examined the role played by the Trp hydroxylase/5-hydroxytryptamine (5-HT) pathway in calibrating host and microbial Trp metabolism during Aspergillus fumigatus pneumonia. We found that 5-HT produced by mast cells essentially contributed to pathogen clearance and immune homeostasis in infection by promoting the host protective indoleamine-2,3-dioxygenase 1/kynurenine pathway and limiting the microbial activation of the indole/aryl hydrocarbon receptor pathway. This occurred via regulation of lung and intestinal microbiota and signaling pathways. 5-HT was deficient in the sputa of patients with Cystic fibrosis, while 5-HT supplementation restored the dysregulated Trp partitioning in murine disease. These findings suggest that 5-HT, by bridging host-microbiota Trp partitioning, may have clinical effects beyond its mood regulatory function in respiratory pathologies with an inflammatory component.
Keyphrases
- microbial community
- amino acid
- end stage renal disease
- signaling pathway
- ejection fraction
- chronic kidney disease
- newly diagnosed
- bipolar disorder
- oxidative stress
- epithelial mesenchymal transition
- depressive symptoms
- cell proliferation
- intensive care unit
- pi k akt
- respiratory failure
- community acquired pneumonia
- mechanical ventilation