What is already known
Alzheimer’s disease is a widespread form of dementia with multiple causes. The link between Alzheimer and periodontitis is just a hypothesis and this hypothesis remains controversial, yet with potential involvement of the oral microbiota.
What this research adds
The review aims to gather 26 studies focused on the relationship between the oral cavity microbiome and Alzheimer’s disease through a genetic approach.
Periodontitis might be associated with cognitive decline, suggesting a possible etiopathologic role in Alzheimer’s disease. However, the contribution of the microbiome remains uncertain, pending more targeted and large-scale studies.
The periodontal infection known as periodontitis could be a predisposing factor for Alzheimer’s disease, since it is associated with cognitive decline. However, its role remains to be further investigated, although the oral microbiota is altered in the presence of the disease.
This is the conclusion of a review conducted by Samantha Mao of Sijhih Cathay General Hospital in New Taipei, Taiwan, published in the Journal of Dental Sciences.
Alzheimer’s disease and oral and gut microbiota
There are more than 55 million cases of Alzheimer‘s disease worldwide, accounting for 50-60% of all dementia cases.
Multiple risk factors certainly include age and genetic predisposition, but also concomitant inflammatory and/or immune-based diseases.
In addition, the hypothesis has recently been compounded that an altered gut microbiome, going to insist on the gut-brain axis, may play a role in the etiopathogenesis of the disease.
Indeed, bacterial metabolites such as LPS or short-chain fatty acids (SCFAs) have been shown to be able to modulate the central and peripheral nervous system by acting as a potential pathogenic link between the gut microbiota and amyloid plaque deposition typical of AD.
The gut microbiota is not the only one involved. In fact, the oral cavity is the second largest distribution of microorganisms, after the intestine (for that matter).
The axis thus, extends becoming gut-mouth-brain going to support the possible association between local and brain-level pathologies.
Periodontitis, an inflammation affecting the gums, has shown some correlation with Alzheimer’s disease especially in more advanced stages, where there is a generalized involvement of the immune system associated with local dysbiosis.
Therefore, in this review, genetic studies (next-generation-sequencing; n= 26) were selected with the aim of exploring the relationship between oral microbiome and Alzheimer’s disease. Let us have a look at the outcomes.
What does emerge from the studies?
Starting from database or questionnaire-based studies (n=6), it was demonstrated that:
- Campylobacter rectus and P. gingivalis showed an association with elevated risk of Alzheimer’s disease. Similar trend for patients with high levels of antibodies to Actinomyces naeslundii.
- P. gingivalis, Prevotella melaninogenenica, Streptococcus oralis, and Staphylococcus intermedius, on the other hand, showed a correlation with increased risk of mortality.
- The gingival pathogens P. intermedia, C. rectus, P. nigrescens, P. melaninogenenica, and P. gingivalis would appear to interact synergistically with H. pylori in promoting the incidence of Alzheimer’s disease.
- High antibodies against Eubacterium nodatum would instead appear to decrease the risk of incurring Alzheimer’s disease.
However, other studies have focused on the connection between Alzheimer’s disease and clinical periodontal and serum parameters:
- Worse cognitive status showed, in general, association with tooth loss and alveolar bed issues.
- Sochocka et al. showed that inflammatory markers such as IL-1β, IL-6, IL-10, and TNF-ⲁ were higher in subjects with Alzheimer’s than in healthy controls. Normal levels of IL-1β and IL-6 for Ide et al., instead.
- Patients with Alzheimer’s disease, albeit with some conflicting results, would seem to be more likely to express IgG antibodies against Aggregatibacter actinomycetemcomitans, P. gingivalis, and Tannerella forsythia.
- Significantly higher levels of P. intermedia and Fusobacterium nucleatum in patients even before actual diagnosis.
Microbiological data, on the other hand, show that:
- Periodontal pathogens P. gingivalis and T. denticola are associated with Alzheimer’s according to Leblhuber et al. No association instead for Laugisch et al.
- Alzheimer’s patients have higher bacterial diversity according to Holmer et al., no significant difference instead for other studies.
- Actinomyces and Rothia are the most abundant species in healthy controls, Slackia exigua, Lachnospiraceae and Prevotella oulorum in the Alzheimer’s group (Holmer et al.); Wu et al. shows instead that Firmicutes, Lactobacillales, Actinomycetales and Veillonellales are the most expressed in subjects with moderate cognitive impairment (MCI), Fusobacteria, Bacteroidetes and Cardiobacteriales in controls; for Yang et al., Pasteurellaceae characterizes instead the MCI group, Lautropia mirabilis the controls; Liu et al. finally demonstrates a predominance of Moraxella, Leptotrichia and Sphaerochaeta in AD patients, Rothia in controls.
In conclusion, postmortem studies show:
- Actinobacteria are more present in the Alzheimer’s group, Proteobacteria in controls.
- P. gingivalis and Treponema were found to be present in the brain of Alzheimer’s patients, not in controls
To sum up, epidemiological-database and postmortem studies seem to confirm an association between periodontal pathogens and Alzheimer’s disease. However, there are incongruent results with genetic data, probably due to a different protocol for sampling and parameters for assessing cognitive status.
Also, it is important to consider how the controls included in these studies may already have undiagnosed cognitive decline. Further studies, including those providing periodontal treatment, are therefore needed to better clarify the relationship between Alzheimer’s to periodontal diseases.