Inflammatory Bowel Disease and Neurodegenerative Diseases

Abstract

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.

Keywords: Dementia; Gut-brain axis; Inflammatory bowel diseases; Multiple sclerosis; Parkinson disease.

Fig. 1

The gut microbiome produces molecules such as SCFAs and 2-BAs that simulate enterochromaffin cells to release 5-HTs. 5-HTs communicate via the vagus nerve, traveling to the nucleus tractus solitarius in the brainstem. The autonomic nervous system also communicates via the vagus nerve and can activate enterochromaffin cells to release 5-HT into the gut. SCFAs, short-chain fatty acids; 2-BAs, secondary bile acids; 5-HTs, serotonins; DRN, dorsal raphe nucleus; NTS, nucleus tractus solitarii.

Fig. 2

Microbial components such as lipopolysaccharide, flagellin, and bacterial lipoprotein encounter immune cells and activate them. The activated immune cells release pro-inflammatory cytokines and modulators such as IFN-γ, IL-1, IL-6, IL-17, and TNF-α, which alters the gut epithelium and blood-brain barrier, leading to increased intestinal and blood-brain barrier permeability. IFN-γ, interferon gamma; IL, interleukin; TNF-α, tumor necrosis factor alpha.