Why Does Oral Microbiome Diversity Correlate with Late Life Cognitive Function?
As the authors of today's open access paper note, their study is not the first to find a correlation between the diversity of the oral microbiome and cognitive function. The relative numbers of different microbial species present in the mouth can be assessed using 16S rRNA sequencing, where different species have slightly different 16S rRNA gene sequences. Given low cost assays to categorize a microbiome, there is a growing interest in the contributions to function and dysfunction made by the various distinct microbiomes situated throughout the body: gut, skin, mouth, and so forth. In this case, a greater diversity of microbial species present in the mouth correlates with a lesser age-related loss of cognitive function. Why is this the case?
The most well researched mechanism is inflammation generated by harmful species such as Porphyromonas gingivalis, responsible for gum disease. Gum disease allows leakage of bacteria and their products into the bloodstream. There is some evidence for this mechanism to underlie a relationship between gum disease and more serious issues such as atherosclerosis and dementia, though there is some debate over whether this is in fact a sizable effect versus other contributing factors. It is possible to speculate in other directions, however. For example, people who take worse care of their oral health probably also undertake less day to day maintenance of health and fitness in other ways, leading to greater age-related neurodegeneration. Or that age-related loss of cognitive function may contribute to a lesser effort in maintaining oral health. The challenge with human epidemiological data is that it does not show causation.
Association of the oral microbiome with cognitive function among older adults: NHANES 2011-2012
An association between the gut microbiome and cognitive function has been demonstrated in prior studies. However, whether the oral microbiome, the second largest microbial habitant in humans, has a role in cognition remains unclear. Using weighted data from the 2011 to 2012 National Health and Nutrition Examination Survey, we examined the association between oral microbial composition and cognitive function in older adults. The oral microbiome was characterized by 16S ribosomal RNA gene sequencing. Cognitive status was assessed using the Consortium to Establish a Registry for Alzheimer's Disease immediate recall and delayed recall, Animal Fluency Test, and Digit Symbol Substitution Test (DSST). Subjective memory changes over 12 months were also assessed. Linear regression and logistic regression models were conducted to quantify the association of α-diversity with different cognitive measurements controlling for potential confounding variables. Differences in β-diversity were analyzed using permutational analysis of variance.
A total of 605 participants aged 60-69 years were included in the analysis. Oral microbial α-diversity was significantly and positively correlated with DSST (β = 2.92). Participants with higher oral microbial α-diversity were more likely to have better cognitive performance status based on DSST (adjusted odds ratio = 2.35) and were less likely to experience subjective memory changes (adjusted odds ratio = 0.43). In addition, β-diversity was statistically significant for the cognitive performance status based on DSST and subjective memory changes.
One potential mechanism underlying oral microbial dysbiosis and cognitive function impairment is systemic inflammation. A recent meta-analysis concluded that the concentrations of plasma or cerebrospinal fluid inflammatory markers were higher in patients with mild cognitive impairment than in normal control individuals. Indeed, alternations in the oral microbiome, a potential source of low-grade systemic inflammation, may contribute to the development of cognitive impairment and dementia. Periodontal disease, a condition known to be linked to oral microbial dysbiosis, has been correlated with elevated levels of neutrophil counts as well as proinflammatory mediators, such as interleukin (IL)-1, IL-6, and C-reactive protein in the blood. Conversely, intensive periodontal treatment resulted in an attenuation of systemic inflammatory markers.
Would a fecal transplant meant to improve the gut microbiome also theoretically improve the oral microbiome? If not, what would?
Yes, there is evidence that the gut microbiome regulates the oral microbiome, as well as systemic inflammation, etc. So FMT (fecal transplant) seems like a reasonable intervention for this.