Oral microbiome–metabolome axis links glycerophospholipid dysregulation to Alzheimer’s disease

Introduction This study aimed to evaluate the feasibility of using tongue biofilm as a non-invasive, patient-friendly, and cost-effective biomarker source for identifying early microbial and metabolic disturbances associated with Alzheimer’s disease (AD).Materials and methods A total of 62 outpatients were enrolled (31 with AD and 31 cognitively normal controls). Tongue biofilm samples were analyzed using 16S rRNA sequencing and untargeted metabolomics via UPLC-Q/TOF-MS. Additionally, cerebrospinal fluid (CSF) samples from 36 individuals (18 per group) were examined under identical untargeted metabolomics processing protocols to validate the metabolomic findings.Results and discussion Microbiome analysis revealed an increased relative abundance of Proteobacteria in the AD group, while Firmicutes and Bacteroidetes were enriched in controls. Metabolomic profiling identified 88 significantly different metabolites between groups, 64 of which achieved area under the curve (AUC) values > 0.90 in the ROC analysis. Glycerophospholipid metabolism has emerged as a key dysregulated pathway in AD, a finding further corroborated by CSF metabolomic analysis. Tongue biofilm represents a non-invasive, cost-effective, and accessible biomarker source, offering potential for AD diagnosis and research when coupled with microbiome and metabolomic analyses. Moreover, the role of glycerophospholipid metabolism in AD pathogenesis warrants further investigation.