Authors: Darbaz Adnan, Phillip A. Engen, Michelle Villanueva, Shohreh Raeisi, Vivian Ramirez, Ankur Naqib, Stefan J. Green, Faraz Bishehsari, Lisa L. Barnes, Ali Keshavarzian, Klodian Dhana & Robin M. Voigt
Journal Reference (Harvard): Adnan, D., Engen, P.A., Villanueva, M., Raeisi, S., Ramirez, V., Naqib, A., Green, S.J., Bishehsari, F., Barnes, L.L., Keshavarzian, A., Dhana, K. and Voigt, R.M. (2025). Oral microbiome brain axis and cognitive performance in older adults. npj Dementia, [online] 1(1). doi:https://doi.org/10.1038/s44400-025-00004-4.
Aim
To evaluate the relationship between oral microbiota diversity in lingual, buccal and salivary niches and cognitive function in participants of advanced age.
Background
The oral microbiota is a composition of microorganisms in the lingual, buccal and salivary niches. Alzheimer’s disease is a neurodegenerative condition resulting in the progressive loss of cognitive function. Genetics, lifestyle, the environment and oral health each play a role in its development. Individuals with no/few teeth due to periodontitis are more susceptible to developing dementia, and experiencing faster progression. Patients with Alzheimer’s disease have distinct oral microbiomes, including increased levels of antibodies against Porphyromonas gingivalis and increased abundance of periopathogens like Treponema denticola and Parvimonas micra.
Methods
A cross-sectional study was carried out using older adults in the MIND trial to assess their oral microbiome niches and cognition, inflammation, AD biomarkers, and brain structure. 143 adults who completed the 3-year cognitive assessments participated. They fasted overnight and avoided performing oral hygiene. Saliva and buccal samples were then taken using a cotton-tipped swab and oral microbiota was sequenced using PCR. Fasting blood samples were collected to assess for AD biomarkers, notably NF-L and Aβ, and inflammatory markers including LBP and IL-6. Cognition was assessed via 12 performance-based tests involving: executive function, perceptual speed, episodic memory and semantic memory. Results were converted into Z Scores consisting of 4 quartiles, from Q1 (lowest) to Q4 (highest).
Results
Individuals with a Q1 cognitive Z-score had an elevated abundance of putative pro-inflammatory bacteria, with reduced Gemella genus, linked to optimal performance. An increased abundance in periopathogens was seen among participants with a Q1 score, as seen in Fig. 1. Salivary Gemella and Treponema were positively correlated with LBP, involved in immunity to Gram-negative bacteria present in AD. Salivary Tannerella was also positively correlated with oxidised LDL, whilst Gemella positively correlated with HDL, also associated with AD. Salivary Phocaeicola was positively correlated with the neurodegeneration marker NF-L.
Fig. 1: Box plots demonstrating the differential abundance of genera in the oral cavity by cognitive Z score for each niche. Parvimonas, Treponema, Filifactor and Eubacterium_yurii_group were all significantly different across each niche.
Conclusions
This study suggests that the oral microbiota may impact cognitive function through influencing cardio-metabolic health, systemic inflammation, promoting gut microbiota dysbiosis and direct invasion of the brain, as seen with Treponema. However, it failed to explore other factors impacting AD risk, notably oral hygiene, lifestyle factors and race. Furthermore, cross sectional study findings only highlight correlations, and may not suggest a causal relationship. Further research is required to assess the relationships in this study in order to determine whether the oral microbiome can function as preclinical biomarkers for Alzheimer’s disease in the future.
Research Summary Written By: Neda Moosavi, University of Manchester – BDS 3