From the gut to the brain: Potential novel avenues for IBD treatment via serotonergic pathways

Inflammatory bowel disease (IBD) is an idiopathic condition characterised by chronic relapsing intestinal inflammation, affecting approximately 6.8 million people globally. Crohn's disease and ulcerative colitis are two main subtypes. The microbiota in IBD patients has been extensively researched, and dysbiosis is associated with IBD onset. While current treatments reduce morbidity and improve the quality of life of IBD patients, they have strong anti-inflammatory effects, creating an immunosuppressed environment and increase the risk of comorbidities, highlighting the need for better therapeutics. The gut-brain axis (GBA) communication pathway allows bidirectional neural, hormonal, metabolic, immunological and microbial signalling. This review investigates the signalling pathways across the GBA and explores how dysbiosis, neuroinflammation and serotonergic dysregulation are interlinked and may contribute to IBD pathogenesis and neurological comorbidities. Focusing on the immunomodulation of serotonergic signalling and proposed mechanisms of action of psychotropic drugs, including antidepressants and psychedelic compounds, we highlight the serotonergic signalling pathway as a potential novel therapeutic target for IBD combination therapy.