The Gut–Immune–Brain Axis: An Important Route for Neuropsychiatric Morbidity in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) comprises Crohn’s disease (CD) and ulcerative colitis (UC) and is associated with neuropsychiatric symptoms like anxiety and depression. Both conditions strongly worsen IBD disease burden. In the present review, we summarize the current understanding of the pathogenesis of depression and anxiety in IBD. We present a stepwise cascade along a gut–immune–brain axis initiated by evasion of chronic intestinal inflammation to pass the epithelial and vascular barrier in the gut and cause systemic inflammation. We then summarize different anatomical transmission routes of gut-derived peripheral inflammation into the central nervous system (CNS) and highlight the current knowledge on neuroinflammatory changes in the CNS of preclinical IBD mouse models with a focus on microglia, the brain-resident macrophages. Subsequently, we discuss how neuroinflammation in IBD can alter neuronal circuitry to trigger symptoms like depression and anxiety. Finally, the role of intestinal microbiota in the gut–immune–brain axis in IBD will be reviewed. A more comprehensive understanding of the interaction between the gastrointestinal tract, the immune system and the CNS accounting for the similarities and differences between UC and CD will pave the path for improved prediction and treatment of neuropsychiatric comorbidities in IBD and other inflammatory diseases.

Dangers of the chronic stress response in the context of the microbiota-gut-immune-brain axis and mental health: a narrative review

“…Recently, novel research questions are exploring the role of microbiome-induced autoimmunity as a novel pathoetiological factor, primarily involving intestinal hyperpermeability, dysbiosis, toll-like receptor (TLR) ligands, and B cell dysfunction, as well as potential therapeutic implications ( 70 ). Altered microbial composition and this inflammatory-dysbiosis-autoimmune process has been identified in a number of autoimmune diseases, such as IBD, multiple sclerosis, lupus, rheumatoid arthritis, and type I diabetes ( 69 , 71 – 74 ). This lends further credence to the common neuropsychiatric comorbidities in autoimmune and other inflammatory states ( 71 ).…”

“…Altered microbial composition and this inflammatory-dysbiosis-autoimmune process has been identified in a number of autoimmune diseases, such as IBD, multiple sclerosis, lupus, rheumatoid arthritis, and type I diabetes ( 69 , 71 – 74 ). This lends further credence to the common neuropsychiatric comorbidities in autoimmune and other inflammatory states ( 71 ). A predominance of Th1/Th17 lymphocytes, plasma cells, and antigen presenting cells (APCs) can instigate the process by presenting luminal microbiota-derived antigens and toxins to T and B lymphocytes, which then become inappropriately activated in autoimmune states ( 69 ).…”

Rosiglitazone Does Not Affect the Risk of Inflammatory Bowel Disease: A Retrospective Cohort Study in Taiwanese Type 2 Diabetes Patients

“…Extraintestinal involvement of skin, joints, eyes, liver, bile ducts, kidney, bone, and cardiovascular system can be seen in up to half of the patients [ 4 , 9 , 10 , 11 ]. Furthermore, IBD may increase the risk of colorectal cancer [ 12 , 13 ] and patients with IBD may have a higher incidence of atherosclerotic cardiovascular diseases, heart failure, atrial fibrillation [ 14 ], psoriasis [ 15 ], Alzheimer’s disease [ 16 , 17 ], depression, and anxiety [ 18 , 19 , 20 ].…”

The Microbiota–Gut–Brain Axis in Behaviour and Brain Disorders

“…The review by Masanetz et al [5] proposes the gut-immune-brain axis as the underlying anatomical and functional route leading to depression and other neuropsychiatric symptoms in inflammatory bowel disease (IBD). The authors reviewed the current understanding of IBD pathophysiology and the development of systemic inflammation in IBD.…”