The potential connection between inflammatory bowel disease and Alzheimer's disease: mechanistic insights and therapeutic implications.

Inflammatory bowel disease (IBD) and Alzheimer's disease (AD) are two chronic conditions previously considered pathologically unrelated. However, accumulating epidemiological evidence suggests that patients with IBD may have an elevated risk. This review systematically analyzes the mechanistic links between IBD and AD, emphasizing the roles of gut microbiota dysbiosis, systemic and neuroinflammation, and glymphatic dysfunction. We propose a putative conceptual framework incorporating the 'gut-glymphatic axis' as a potential conduit through which IBD-associated microbial and immune perturbations may influence AD pathology. Key pathways include short-chain fatty acids, tryptophan metabolites, trimethylamine N-oxide, and bile acids, all of which modulate neuroinflammation and amyloid-β clearance. Additionally, circadian disruption and impaired aquaporin-4 polarity in the glymphatic system may represent novel links between intestinal inflammation and neurodegenerative changes. Preclinical animal models suggest that colitis exacerbates AD-like pathology via NLRP3 inflammasome activation, neutrophil infiltration, and microglial dysfunction. Natural bioactive compounds-such as ginsenosides, curcumin, baicalin, berberine, and magnolol-show dual therapeutic potential in both IBD and AD by targeting shared inflammatory and microbiota pathways. However, validated comorbidity models and clinical trials are lacking. This review provides a scientifically grounded basis for future mechanistic studies and integrated interventions for IBD-AD comorbidity.