Surprising link between a diverse oral microbiome and better cognitive function in aging

By Pooja Toshniwal PahariaReviewed by Susha Cheriyedath, M.Sc.Jun 9 2024

In a recent study published in The Journal of Nutrition, Health, and Aging, researchers determined the association between the oral microbiome and cognition among older United States (US) adults.

Study: Association of the oral microbiome with cognitive function among older adults: NHANES 2011–2012. Image Credit: ESB Professional / Shutterstock

Background

Cognitive impairment and dementia are serious health challenges in aging populations, with dementia defined as a gradual loss of cognition function. Identifying risk factors related to cognitive impairment is critical for lowering the dementia burden. Previous research has revealed a link between the gut microbiome and cognition performance, with the mouth cavity housing the second-largest microbial population in humans. However, the effect of the oral microbiota on cognition remains unknown.

Oral microbial communities are crucial to physiological and immunological activities such as ambient chemical processing and detoxification, immune system maintenance, and disease prevention. Small-scale clinical investigations on the relationship between the oral microbiome and Alzheimer's disease have produced inconsistent results, with some reporting lower oral microbial diversity in AD patients and others not.

About the study

In the present study, researchers investigated whether oral microbes are associated with cognition function among adults aged 60 to 69.

The team analyzed the 2011–2012 National Health and Nutrition Examination Survey (NHANES) cross-sectional data. Participants provided oral rinse samples, from which the researchers extracted deoxyribonucleic acid (DNA) for polymerase chain reaction (PCR) and sequencing. Researchers characterized the oral microbiota based on 16S ribosomal ribonucleic acid (RNA) sequencing.

The cognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)- Delayed Recall (DR) and Immediate Recall (IR), Digit Symbol Substitution Test (DSST), and Animal Fluency Test (AFT). The researchers also assessed subjective memory alterations over a year. They used multivariate logistic regressions to determine the odds ratios (OR) for the relationship between alpha diversity and the cognitive measures.

The researchers analyzed beta diversity differences using permutational multivariate analysis of variance (PERMANOVA). They applied observed amplicon sequence variants (ASVs), the estimation of species richness, as the metric of the alpha diversity index. Beta diversity evaluation compared microbial community structures between groups.

Study covariates included age, biological sex, race, body mass index, educational attainment, poverty status, alcohol intake, smoking status, physical activity, diabetes, and hypertension. The researchers assessed poverty using the poverty-income ratio (PIR) and physical activity using the Global Physical Activity Questionnaire. They determined stroke history using the Medical Condition Questionnaire.

Results and discussion

The study included 605 individuals with a mean age of 64; 77% were non-Hispanic Whites, and 70% had attained high school education. The mean CERAD-DR, CERAD-IR, DSST, and AFT scores were 6.40, 20, 58, and 20, respectively. The researchers observed lower cognitive scores among older and physically less active individuals with lower educational attainment, family income, pre-existing hypertension, and diabetes who smoked in current times.

Oral microbial alpha diversity showed significant and positive correlations with DSST. Individuals with higher alpha diversity in their oral microbiome showed a higher likelihood of better cognitive function evaluated using DSST (adjusted OR, 2.4) and a lower likelihood of experiencing subjective alterations in memory (adjusted OR, 0.4). Additionally, beta diversity showed statistically significant associations for cognitive performances determined using DSST and subjective changes in memory.

Oral microbial dysbiosis and cognitive function impairment may be associated with systemic inflammation, with individuals with moderate cognitive impairment exhibiting greater inflammatory levels. Alterations in the oral microbiota may lead to cognitive decline and dementia. Periodontal disease, caused by oral microbial dysbiosis, has been associated with high neutrophil numbers and proinflammatory mediators. However, extensive periodontal therapy can lower systemic inflammatory indicators. Campylobacter rectus and Porphyromonas gingivalis titers are associated with Alzheimer's disease incidence.

Conclusions

The study showed that oral microbiota is associated with subjective memory and executive function among older individuals residing in the United States, supporting the "oral-brain axis." The oral microbiome's alpha diversity was strongly related to the DSST, an executive function test. Health behaviors such as dental cleanliness, smoking, and food can influence the oral microbiome. Such factors may lead to novel approaches to aging-related cognitive loss, such as discovering biomarkers for risk assessment, developing treatments, and reducing comorbidities.

However, larger human sample sizes and long-term investigations are required to corroborate these results. The study also implies that oral dysbiosis affects executive function more than verbal memory, making it a potential biomarker or treatment target for cognition decay. Further research is required to understand the processes behind these relationships and the cognitive areas most influenced by the oral microbiota.