Introduction
Inflammatory bowel diseases (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), are chronic gastrointestinal disorders accompanied by psychiatric comorbidities, particularly anxiety and depression. The link between IBD and anxiety and depression remains unclear, but it appears that, among others, it may be explained by altered tryptophan metabolism. Tryptophan, an essential amino acid, is crucial for maintaining mental health and regulating mood through its metabolic processes. It serves as a precursor for several biologically significant compounds, including serotonin, melatonin, and kynurenine metabolites. The interplay between inflammation, tryptophan metabolism, and mental health in IBD remains insufficiently explored.
Aims & Methods
This study aimed to assess the association between metabolites of the tryptophan-kynurenine pathway and depressive symptoms in IBD regarding the disease activity and phenotype. A cohort of 214 patients with IBD (70 with CD and 144 with UC) was included. Disease activity was determined using the Mayo score for UC and SES-CD for CD. Peripheral blood samples were analyzed for selected biomarkers, including metabolites of tryptophan-kynurenine pathway as well as indicators of oxidative stress and inflammation. Depressive symptoms were evaluated using the Beck Depression Inventory (BDI). Statistical analyses included correlation and regression models to explore the relationship between biomarkers and BDI scores, adjusting for clinical and demographic covariates.
Results
The BDI score in the study group ranged from 0 to 52. 31 individuals met the criteria for depression by scoring over 10 points. 137 patients with active disease exhibited significantly higher levels of hsCRP and nitrotyrosine and lower kynurenic acid levels compared to 77 with inactive disease. Kynurenic acid levels were negatively correlated with BDI scores (r = -0.220, p = 0.042), suggesting an association between tryptophan metabolism and depressive symptoms. Additionally, CD patients showed higher serotonin and anthranilic acid levels compared to UC patients (16.67 ± 26.23 vs 6.29 ± 12.55 and 0.35 ± 0.26 vs 0.17 ± 0.17, respectively), though no significant differences in BDI scores were observed between the groups. Biological treatment was more frequent in the active disease group and associated with higher BDI scores, even after adjusting for covariates.
Table 1. Comparison of selected metabolite levels between individuals with active disease and with inactive disease
| Active disease | Inactive disease | p |
| Chlorotyrosine, nM | 0.35 ± 0.41 | 0.26 ± 0.45 | 0.222 |
| Nitrotyrosine, nM | 0.38 ± 0.20 | 0.26 ± 0.17 | 0.043 |
| Bromotyrosine, nM | 0.05 ± 0.06 | 0.03 ± 0.03 | 0.553 |
| L-tryptophan, M | 54.67 ± 15.79 | 60.98 ± 15.34 | 0.117 |
| L-kynurenine, M | 3.53 ± 1.22 | 3.48 ± 1.01 | 0.680 |
| 5-hydroxy-L-trypthophan, M | 0.20 ± 0.15 | 0.23 ± 0.13 | 0.233 |
| 3-indolepropionic acid, M | 0.33 ± 0.57 | 0.20 ± 0.21 | 0.723 |
| 3-indoleacyrylic acid, M | 2.31 ± 0.66 | 2.46 ± 0.54 | 0.322 |
| Kynurenic acid, M | 0.06 ± 0.04 | 0.08 ± 0.03 | 0.035 |
Data expressed as n (%) or mean ± SD.
Significant between-group differences (p < 0.05) are marked in bold.
Conclusion
The study revealed significant differences in the tryptophan-kynurenine metabolic pathway among patients with inflammatory bowel disease, which vary based on disease activity. Additionally, variations in the concentrations of certain metabolites are correlated with the severity of depression.
References
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