Gut–Brain Axis in Inflammatory Bowel Disease: Pathogenesis and Therapeutics

Author(s): Samantha Perry, Lekha Pillarisetti, Tamara Gelfman, Devendra K. Agrawal

Inflammatory Bowel Disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract driven by complex interactions between genetic susceptibility, environmental triggers, microbial dysbiosis, and immune dysregulation. The gut microbiome, composed primarily of Firmicutes and Bacteroidetes, plays a crucial role in maintaining intestinal barrier integrity, immune balance, and neuroimmune signaling. Disruption of this microbial ecosystem is characterized by loss of beneficial short chain fatty acid producing bacteria and expansion of pathogenic species which promotes mucosal inflammation, cytokine release, and neuroimmune signaling that can disrupt mental health through the gut-brain axis. Emerging evidence links microbial metabolites, vagal tone, and the hypothalamic-pituitaryadrenal axis in a feedback loop that perpetuates inflammation and alters mood regulation. Current therapeutic approaches include diet modification, osteopathic manipulative treatments, fecal microbiota transplantation and phage therapy. This article focuses on understanding mechanisms linking dysbiosis, immune activation, and neuroinflammation to guide future interventions. A holistic model addressing the gut-brain axis holds the greatest promise for improving outcomes and personalizing care for IBD.