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

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.

Automated summary

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract and is often accompanied by depressive symptoms. The dysregulated immune response and neuroglial dysfunction play important roles in the development of chronic inflammation and depression. The kynurenine pathway (KP) is a significant metabolite pathway that regulates chronic inflammation and depressive symptoms. KP metabolites, especially quinolinic acid, accumulate in the brain and contribute to the comorbidity of IBD and depression. This review summarizes the pathological mechanisms of KP metabolite-mediated chronic intestinal inflammation and depressive symptoms by regulating the immune response.