Accumulating evidence indicates that helicobacter pylori (HP) is related to Alzheimer's disease (AD).
Objective
To investigate the roles of HP on the pathogenesis of AD involving gut-brain axis dysfunction and blood-brain barrier (BBB) disruption.
Methods
Total 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.
Results
AD-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).
Conclusions
HP infection exacerbates gut dysbiosis, promotes BBB disruption, intensifies neuroinflammation, accelerates AD pathology, and aggravates cognitive decline.
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