Abstract
BACKGROUND: Chronic inflammatory diseases (CIDs) are systems disorders that affect diverse organs including the intestine, joints and skin. The essential amino acid tryptophan (Trp) can be broken down to various bioactive derivatives important for immune regulation. Increased Trp catabolism has been observed in some CIDs, so we aimed to characterise the specificity and extent of Trp degradation as a systems phenomenon across CIDs.
METHODS: We used high performance liquid chromatography and targeted mass spectrometry to assess the serum and stool levels of Trp and Trp derivatives. Our retrospective study incorporates both cross-sectional and longitudinal components, as we have included a healthy population as a reference and there are also multiple observations per patient over time.
FINDINGS: We found reduced serum Trp levels across the majority of CIDs, and a prevailing negative relationship between Trp and systemic inflammatory marker C-reactive protein (CRP). Notably, serum Trp was low in several CIDs even in the absence of measurable systemic inflammation. Increases in the kynurenine-to-Trp ratio (Kyn:Trp) suggest that these changes result from increased degradation along the kynurenine pathway.
INTERPRETATION: Increases in Kyn:Trp indicate the kynurenine pathway as a major route for CID-related Trp metabolism disruption and the specificity of the network changes indicates excessive Trp degradation relative to other proteogenic amino acids. Our results suggest that increased Trp catabolism is a common metabolic occurrence in CIDs that may directly affect systemic immunity.
FUNDING: This work was supported by the DFG Cluster of Excellence 2167 "Precision medicine in chronic inflammation" (KA, SSchr, PR, BH, SWa), the BMBF (e:Med Juniorverbund "Try-IBD" 01ZX1915A and 01ZX2215, the e:Med Network iTREAT 01ZX2202A, and GUIDE-IBD 031L0188A), EKFS (2020_EKCS.11, KA), DFG RU5042 (PR, KA), and Innovative Medicines Initiative 2 Joint Undertakings ("Taxonomy, Treatments, Targets and Remission", 831434, "ImmUniverse", 853995, "BIOMAP", 821511).
| Original language | English |
|---|---|
| Article number | 105056 |
| Journal | eBioMedicine |
| Volume | 102 |
| Pages (from-to) | 105056 |
| DOIs | |
| Publication status | Published - 04.2024 |
Funding
The authors would like to thank the patients of the University Medical Center Schleswig–Holstein for making our work possible. The popgen 2.0 network provided biomaterial and data handling support. The popgen 2.0 network (P2N) is supported by the Medical Faculty of the University of Kiel. This work was supported by the DFG Cluster of Excellence 2167 “Precision medicine in chronic inflammation”, the BMBF (e:Med Juniorverbund “Try-IBD” 01ZX1915A and 01ZX2215, the e:Med Network iTREAT 01ZX2202A, and GUIDE-IBD 031L0188A), EKFS (2020_EKCS.11, KA), DFG RU5042, and Innovative Medicine Initiative 2 Joint Undertakings (“Taxonomy, Treatments, Targets and Remission”, 831434, “ImmUniverse”, 853995, “BIOMAP”, 821511).
| Funders | Funder number |
|---|---|
| University of Kiel | |
| Deutsche Forschungsgemeinschaft | |
| Bundesministerium für Bildung und Forschung | 01ZX1915A, 01ZX2202A, GUIDE-IBD 031L0188A, 01ZX2215 |
| Bundesministerium für Bildung und Forschung | |
| Else Kröner-Fresenius-Stiftung | 2020_EKCS.11, RU5042 |
| Else Kröner-Fresenius-Stiftung | |
| Innovative Medicines Initiative | 821511, 831434, 853995 |
| Innovative Medicines Initiative |
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
DFG Research Classification Scheme
- 2.21-05 Immunology
