Analysis of Salivary Microbiome in Patients with Alzheimer’s Disease Original paper

What was studied?

This study investigated the salivary microbiome in Alzheimer’s disease, focusing on how oral microbial composition differs between patients with Alzheimer’s disease (AD) and cognitively healthy adults. Using 16S rRNA gene sequencing, the researchers profiled bacterial richness, diversity, and taxonomic distribution in saliva, while also examining whether APOE4 genotype or clinical severity influenced microbial patterns. The authors contextualised this work within growing evidence that oral bacteria can migrate to the brain, potentially contributing to amyloid plaque formation, neuroinflammation, and blood–brain barrier disruption. By profiling oral bacteria—more accessible than other microbial habitats—the study aimed to clarify whether AD is associated with distinct salivary microbial signatures that may serve as biomarkers or mechanistic clues relevant to neurodegeneration.

Who was studied?

Seventy-eight adults participated, including 39 AD patients and 39 healthy controls, all recruited from Xiangya Hospital in China. Controls were spouses or cohabitants of AD patients to minimise dietary and environmental differences. All participants were screened to exclude recent antibiotic use, alcohol consumption, oral infections, dental procedures, systemic disease, or other neurodegenerative conditions. AD diagnoses followed NINCDS-ADRDA criteria confirmed by multiple neurologists. Patients were stratified by cognitive severity using MMSE and by APOE4 carrier status through Sanger sequencing. Saliva samples were collected under standardised conditions, ensuring high-quality microbial DNA for sequencing.

Most important findings

The study revealed a marked reduction in microbial richness and diversity in AD saliva, demonstrated through significantly lower Chao1, Shannon, and PD whole-tree indices. Despite similar phylum-level composition between groups, several genera displayed disease-related shifts. Moraxella, Leptotrichia, and Sphaerochaeta were significantly enriched in AD, whereas Rothia was more abundant among controls. These taxa include Gram-negative species and bacteria with functional amyloids capable of interacting with neural tissue. APOE4-related differences were also detected. Carriers exhibited higher levels of Abiotrophia and Desulfomicrobium, while Actinobacillus and Actinomyces were reduced. No taxa correlated with AD severity, suggesting microbial alterations may occur independently of clinical stage.

Key implications

These findings support a mechanistic model in which oral dysbiosis may influence neurodegeneration by increasing exposure to bacteria or bacterial products capable of crossing the blood–brain barrier. The enrichment of Gram-negative taxa in AD is notable, as lipopolysaccharide has been detected in amyloid plaques. Reduced microbial diversity may destabilise the oral ecosystem, allowing opportunistic species to proliferate and potentially access neural tissue through olfactory or trigeminal pathways. The APOE4-associated differences further imply that genetic susceptibility may interact with microbial factors by altering barrier integrity or immune responses. Clinically, the salivary microbiome offers a non-invasive avenue for biomarker development and may highlight the value of oral health as a modifiable risk factor in dementia prevention.

Citation

Liu XX, Jiao B, Liao XX, et al. Analysis of salivary microbiome in patients with Alzheimer’s disease.Journal of Alzheimer’s Disease. 2019; 10.3233/JAD-190587