Kynurenine pathway metabolites modulated the comorbidity of IBD and depressive symptoms through the immune response

• Published in: International immunopharmacology 2023-04, Vol.117, p.109840-109840, Article 109840
• Main Authors: Lai, Weiming, Huang, Ziheng, Li, Sheng, Li, Xiang-Guang, Luo, Ding
• Format: Article
• Language: English
• Subjects: Colitis, Ulcerative; Comorbidity; Depression; Depressive symptom; Humans; Immune response; Inflammation - metabolism; Inflammatory bowel disease; Kynurenine - metabolism; Kynurenine pathway; Tryptophan - metabolism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.109840

•The immunological mechanism of the comorbidity of IBD and depressive symptoms remains to be revealed. In addition, the ability of kynurenine pathway metabolites to exert anti-inflammation and neuroactive in the comorbidity of IBD and depressive symptoms has raised concerns.•Overexpression of proinflammatory cytokines induces dysregulation of the brain-gut axis, leading to the comorbidity of IBD and depressive symptoms.•It’s appreciated to summarize the therapeutic targets of kynurenine pathway metabolites and extrinsic factors in the comorbidity of IBD and depressive symptoms for proposing a potential therapeutic strategy. Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is defined as chronic inflammation in the gastrointestinal tract. Notably, more than 20% of people with IBD experience depressive symptoms. Understanding the immunological mechanism of chronic intestinal inflammation on cognitive behavior has become a key research focus. Previous studies have shown that a dysregulated immune response contributes to chronic inflammation and depressive symptoms. The tolerant phenotype exhibited by immune cells regulates the course of chronic inflammation in distinct ways. In addition, neuroglia, such as microglia and astrocytes specific to the brain, are also influenced by deregulated inflammation to mediate the development of depressive symptoms. The kynurenine pathway (KP), a significant tryptophan metabolic pathway, transforms tryptophan into a series of KP metabolites that modulate chronic inflammation and depressive symptoms. In particular, indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in the KP, is activated by chronic inflammation and leads to the production of kynurenine. In addition, disruption of the brain-gut axis induced by IBD allows kynurenine to cross the blood–brain barrier (BBB) and form a series of neuroactive kynurenine metabolites in glial cells. Among them, quinolinic acid continuously accumulates in the brain, indicating depression. Thus, KP metabolites are critical for driving the comorbidity of IBD and depressive symptoms. In this review, the pathological mechanism of KP metabolite-mediated chronic intestinal inflammation and depressive symptoms by regulating the immune response is summarized according to the latest reports.