The aryl hydrocarbon receptor and kynurenine pathway: connecting inflammatory bowel disease and depression via the microbiota gut brain axis

Inflammatory bowel disease (IBD) is a disorder characterized by chronic inflammation in the gastrointestinal (GI) tract. This disease has a complex etiology with major contributing factors including genetics, host-microbiome interactions, dysregulation of the immune response, and various environmental triggers. The negative impacts of IBD are not limited to the GI tract however, as IBD patients also develop extraintestinal manifestations involving multiple organs and organ systems. In support of this, IBD patients have increased incidence of mood and behavioral disorders, such as depression, which are often attributed to the concept known as the microbiota gut brain axis (MGBA). This concept refers to the bidirectional communication between the GI tract and central nervous system (CNS) via key components. While it is clear IBD and depression often manifest together, it remains unclear what major mechanisms drive this relationship. Growing evidence suggests that the aryl hydrocarbon receptor (AhR) impacts disease severity in both IBD and behavioral disorders. The purpose of this review is to summarize IBD and depression with emphasis on the potential role AhR plays in both disorders. In addition, evidence of the kynurenine pathway (KP) in IBD and depression will be discussed with particular focus on how this biochemical pathway is linked to both the activation of AhR and its regulation, thus making it an interesting connection requiring further investigation. This review will also summarize key mechanisms of the MGBA implicated in the comorbidity of IBD and depression highlighting the impact, if any, AhR and KP play in these factors. Lastly, the review will discuss limitations of this current topic and any potential future directions to better understand the roles of AhR and KP in comorbid IBD and depression.