Classifying dementia progression using microbial profiling of saliva Original paper

What was studied?

This original research article investigated how the salivary microbiome changes across the continuum of dementia progression, focusing on how microbial signatures—particularly shifts in periodontal and opportunistic oral bacteria—correlate with cognitive decline. The study explored whether specific salivary bacteria could distinguish between cognitively normal individuals, those at risk due to olfactory deficits, individuals with mild cognitive impairment, and patients with Alzheimer’s disease. The goal was to determine whether microbiome-based biomarkers could contribute to a non-invasive, saliva-based staging tool for neurodegeneration and whether these microbial changes provide clinically relevant microbiome signatures of dementia progression.

Who was studied?

The study examined 78 age-matched adults recruited from a memory clinic, segmented into four groups: cognitively normal with normal olfaction (CNh), cognitively normal with reduced olfaction (CNr), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). All participants underwent standardized cognitive testing (MMSE, CDR), olfactory assessment (UPSIT), saliva collection, 16S rRNA microbial profiling, and cytokine analysis. The researchers emphasized the CNr group as clinically intact but olfactorily impaired, positioning them as a potential preclinical risk category preceding cognitive decline. This human cohort provided a cross-sectional snapshot of microbial and immunologic patterns linked to dementia stage.

Most important findings

The salivary microbiome exhibited clear, stage-dependent microbial signatures, even though overall microbial diversity remained stable. Linear discriminant analysis (page 4) showed that microbial profiles distinguished groups with high accuracy, unlike cytokine profiles, which lacked clear stage specificity. The dominant microbiome shift involved a progressive decline in periodontal pathogens, notably Filifactor villosus, across CNr to AD, accompanied by reduced Filifactor alocis, Prevotella tannerae, and Porphyromonas gingivalis. In contrast, the opportunistic species Leptotrichia wadei increased significantly in MCI before declining in AD, suggesting a competitive ecological shift in oral niches. These changes reflect a transition from periodontal dominance to opportunistic colonization in early cognitive impairment. Cytokine changes were minimal but hinted at early synergistic increases in IL-1α and IL-8 in CNr and heightened IL-6 and MIP-1α in MCI, consistent with immune responses to shifting microbial communities. Logistic regression showed moderate predictive value for individual species, with improved performance when combined with olfactory scores (UPSIT), suggesting that microbial biomarkers enhance dementia staging when integrated with sensory testing.

Key implications

These findings support saliva as a viable, non-invasive biofluid for monitoring dementia-related microbial changes. The early decline of periodontal taxa alongside the rise of opportunistic species suggests that oral dysbiosis may precede or accompany neurodegeneration. Incorporating microbial signatures with olfactory testing could enhance early diagnostic accuracy for at-risk individuals before cognitive symptoms emerge. This work strengthens the evidence that microbiome-based classifiers may aid in staging dementia progression and underscores the potential of salivary profiling in clinical settings, particularly for screening and longitudinal monitoring.

Citation

Bathini P, Foucras S, Dupanloup I, et al. Classifying dementia progression using microbial profiling of saliva. Alzheimer’s Dement. 2020;12:e12000. doi:10.1002/dad2.12000