The roles of helicobacter pylori infection on the pathogenesis of Alzheimer's disease: Gut-brain axis dysfunction and blood-brain barrier disruption

BackgroundAccumulating evidence indicates that helicobacter pylori (HP) is related to Alzheimer's disease (AD).ObjectiveTo investigate the roles of HP on the pathogenesis of AD involving gut-brain axis dysfunction and blood-brain barrier (BBB) disruption.MethodsTotal 62 AD patients were categorized into AD with HP (AD-HP) and AD with no (AD-nHP) groups. Demographic and cognitive data were collected, and HP infection was confirmed by ¹³C-urea breath test. The levels of BBB variables, neuroinflammatory factors, and AD biomarkers in cerebrospinal fluid (CSF) were measured using enzyme-linked immunosorbent assay. Gut microbiota and metabolites were profiled by 16S ribosomal ribonucleic acid gene sequencing and gas chromatography-mass spectrometry. Correlations and linear regression among above variables were analyzed.ResultsAD-HP group exhibited impaired overall cognition and cognitive domains of immediate and short-term memory and language, and elevated CSF levels of matrix metallopeptidase (MMP) 9, vascular endothelial growth factor (VEGF), interferon-γ, and phosphorylated tau (P-tau) 181. Overall cognitive score was positively correlated with amyloid-β₄₂ and negatively with P-tau181 levels in CSF. Positive correlations were observed between P-tau181 and soluble triggering receptor expressed on myeloid cells 2, between P-tau231 and chitinase-3-like protein, and between P-tau231 and BBB variables (receptor for advanced glycation endproducts, MMP9, zsonula occludens-1, and claudin-5). In AD-HP group, there was a unique dysbiosis pattern of gut microbiota and metabolites, and HP was particularly associated with the reduced gut 23-nordeoxycholic acid methyl ester and elevated CSF VEGF level (all p < 0.05).ConclusionsHP infection exacerbates gut dysbiosis, promotes BBB disruption, intensifies neuroinflammation, accelerates AD pathology, and aggravates cognitive decline.