Article: Association between the indole pathway of tryptophan metabolism and subclinical depressive symptoms in obesity: a preliminary study

Converging data support the role of chronic low-grade inflammation in depressive symptomatology in obesity. One mechanism likely to be involved relies on the effects of inflammation on tryptophan (TRP) metabolism. While recent data document alterations in the indole pathway of TRP metabolism in obesity, the relevance of this mechanism to obesity-related depressive symptoms has not been investigated. The aim of this preliminary study was to assess the association between plasma levels of TRP and indole metabolites and depressive symptoms in 44 subjects with severe or morbid obesity, free of clinically relevant neuropsychiatric disorders. The interaction effect of inflammation, reflected in serum high-sensitive C-reactive protein (hsCRP) levels, and indoles on depressive symptoms was also determined. Higher serum levels of hsCRP and lower concentrations of TRP and indoles, particularly indole-3-carboxaldehyde (IAld), correlated with more severe depressive symptoms. Interestingly, the effect of high hsCRP levels in predicting greater depressive symptoms was potentiated by low IAld levels. These results comfort the link between inflammation, the indole pathway of TRP metabolism, and obesity-related depressive symptoms.

Citing Articles

Metformin-mediated intestinal AMPK activation ameliorates PCOS through gut microbiota modulation and metabolic pathways.

Xu Y, Ning L, Si Y, Li X, Wang R, Ren Q Front Endocrinol (Lausanne). 2025; 16:1526109.

PMID: 40041289 PMC: 11876036. DOI: 10.3389/fendo.2025.1526109.

Dysregulated tryptophan metabolism contributes to metabolic syndrome in Chinese community-dwelling older adults.

Sun S, Hu F, Sang Y, Wang S, Liu X, Shi J BMC Endocr Disord. 2025; 25(1):7.

PMID: 39780122 PMC: 11708088. DOI: 10.1186/s12902-024-01826-8.

The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies.

Bahmani M, Mehrtabar S, Jafarizadeh A, Zoghi S, Sadeghpour Heravi F, Abbasi A Curr Pharm Biotechnol. 2024; 25(16):2089-2107.

PMID: 38288791 DOI: 10.2174/0113892010281892240116081031.

Determination of tryptophan and its indole metabolites in follicular fluid of women with diminished ovarian reserve.

Liu A, Shen H, Li Q, He J, Wang B, Du W Sci Rep. 2023; 13(1):17124.

PMID: 37816920 PMC: 10564947. DOI: 10.1038/s41598-023-44335-9.

A Preliminary Comparison of Plasma Tryptophan Metabolites and Medium- and Long-Chain Fatty Acids in Adult Patients with Major Depressive Disorder and Schizophrenia.

Liu J, Yu H, Li R, Zhou C, Shi Q, Guo L Medicina (Kaunas). 2023; 59(2).

PMID: 36837614 PMC: 9968143. DOI: 10.3390/medicina59020413.

References

1.

Delgado I, Huet L, Dexpert S, Beau C, Forestier D, Ledaguenel P . Depressive symptoms in obesity: Relative contribution of low-grade inflammation and metabolic health. Psychoneuroendocrinology. 2018; 91:55-61. DOI: 10.1016/j.psyneuen.2018.02.030. View

2.

Capuron L, Miller A . Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011; 130(2):226-38. PMC: 3072299. DOI: 10.1016/j.pharmthera.2011.01.014. View

3.

Raison C, Capuron L, Miller A . Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2005; 27(1):24-31. PMC: 3392963. DOI: 10.1016/j.it.2005.11.006. View

4.

Hunt C, Cordeiro T, Suchting R, de Dios C, Cuellar Leal V, Soares J . Effect of immune activation on the kynurenine pathway and depression symptoms - A systematic review and meta-analysis. Neurosci Biobehav Rev. 2020; 118:514-523. PMC: 8087452. DOI: 10.1016/j.neubiorev.2020.08.010. View

5.

OConnor J, Lawson M, Andre C, Moreau M, Lestage J, Castanon N . Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry. 2008; 14(5):511-22. PMC: 2683474. DOI: 10.1038/sj.mp.4002148. View

6.

Zelante T, Puccetti M, Giovagnoli S, Romani L . Regulation of host physiology and immunity by microbial indole-3-aldehyde. Curr Opin Immunol. 2021; 70:27-32. DOI: 10.1016/j.coi.2020.12.004. View

7.

Arnoriaga-Rodriguez M, Mayneris-Perxachs J, Burokas A, Contreras-Rodriguez O, Blasco G, Coll C . Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids. Cell Metab. 2020; 32(4):548-560.e7. DOI: 10.1016/j.cmet.2020.09.002. View

8.

Montgomery S, Asberg M . A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979; 134:382-9. DOI: 10.1192/bjp.134.4.382. View

9.

Capuron L, Ravaud A, Neveu P, Miller A, Maes M, Dantzer R . Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry. 2002; 7(5):468-73. DOI: 10.1038/sj.mp.4000995. View

10.

Abildgaard A, Elfving B, Hokland M, Wegener G, Lund S . Probiotic treatment reduces depressive-like behaviour in rats independently of diet. Psychoneuroendocrinology. 2017; 79:40-48. DOI: 10.1016/j.psyneuen.2017.02.014. View

11.

Rothhammer V, Mascanfroni I, Bunse L, Takenaka M, Kenison J, Mayo L . Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016; 22(6):586-97. PMC: 4899206. DOI: 10.1038/nm.4106. View

Association Between the Indole Pathway of Tryptophan Metabolism and Subclinical Depressive Symptoms in Obesity: a Preliminary Study