Oral Dysbiosis and Alzheimer’s Disease Risk

The oral microbiome is implicated in many systemic illnesses such as cardiovascular disease, metabolic syndrome, respiratory infections, and cognitive decline, with the common link between them being inflammation.^1-4 A connection between oral health, inflammation, and neurodegenerative conditions such as Alzheimer’s disease (AD) has long been speculated, and recent findings have suggested that chronic bacterial infections from periodontitis may contribute to neurodegenerative processes and thus may be lifelong risk factors for AD development.^5-7

Bacterial communities form biofilm (dental plaque) on teeth and in oral and gingival tissue. High pathogenic load can disrupt the oral microbiome, causing inflammation and dysregulation of the immune system response.⁸ Bacterial overgrowth and chronic inflammation can lead to a variety of local diseases like periodontitis and dental caries, and translocation of this pathogenic bacteria into the bloodstream can reach other organs in the body, including the heart,⁹ liver,^10,11 and brain.¹² In brain tissue, oral bacteria is linked to increased neuroinflammation and damaged neuronal cells, which contributes to cognitive decline and long-latent neurodegenerative pathologies like AD. Assessing and treating a patient’s oral dysbiosis in a clinical setting may help to optimize both mouth and brain health.

AD Risk Factors: Chronic Periodontal Disease & Bacterial Translocation

As the hallmark bacteria of periodontal diseases, Porphyromonas gingivalis (P. gingivalis) has been suggested as a potential microbial driver in AD pathology.¹³ Impacting an estimated 42.7% of adults over 30,¹⁴ periodontal disease manifests as the accumulation of several bacteria in the mouth and the formation of dysbiotic biofilm on oral tissue surfaces. Significant oral pathogenic load contributes to oral microbiome imbalances, greater inflammatory burden on the body, and immune system dysregulation. Because of this, periodontal disease is considered to be a risk factor for AD for any age group, and studies have shown that chronic periodontal disease lasting 10 years or longer increases this risk twofold.^5,16

Periodontal disease is more common in adults over 65, with an estimated occurrence of 70.1% of this population.¹⁴ A recent systematic review associated baseline presence of periodontitis in adults over 65 with a six-fold increase in the rate of cognitive decline over a six-month follow-up period.¹⁵ Increased presence of P. gingivalis in older populations is also associated with greater oral tissue depletion, gingival inflammation, and edentulism.^16,17

A scoping review of the potential mechanisms between periodontitis and AD suggest the direct translocation of periodontal bacteria to the brain induces neuroinflammation and a proinflammatory cytokine response.¹⁸ Altered microbiota in the oral cavity can spread via the lymphatic and vascular systems, infecting tissue in the brain and indirectly contributing to inflammatory pathways through immune system activation.⁵ P. gingivalis can enter the bloodstream and perivascular spaces when localized tissue trauma occurs from brushing, flossing, and chewing, or in cases of gingival bleeding or bacterial permeation of weakened periodontal tissue.⁵ In vivo, P. gingivalis secretes cysteine proteases called gingipains that damage neuronal cells. Immunoreactivity to gingipains is consistent with increased neuroinflammation in AD-afflicted brains as compared to those without, and colonization of P. gingivalis has been documented post-mortem in both human and animal brain studies.¹² Patients with advanced stages of AD are observed to have higher dental plaque weight and more missing teeth than their healthy counterparts. Poor oral hygiene practices are part of the equation and contribute to higher rates of bacterial colonization in the mouth. Due to the nature of AD symptoms, forgetting to maintain oral hygiene results in a greater oral pathogenic load, which may residually accelerate the disease processes in the brain.¹⁷

Nutrition and Probiotics: Not Just for Gut Health

Nutrition is an important consideration for patients experiencing periodontal diseases as several nutrient deficiencies may lead to a dysbiotic oral microbiome.¹⁹ Plant-based diets include key micronutrients that support healthy oral microflora such as vitamin C and D, calcium, phosphorous, fluorine, and nitrite.^19-21 In addition, polyphenols found in certain food sources have anti-inflammatory, anti-oxidative, and demonstrated antibacterial properties against P. gingivalis, including the catechin epigallocatechin-3-gallate found in green tea, curcumin, cranberries, pomegranate, mango, resveratrol from grapes and wine, and rice extracts.^20-23 These polyphenols are also noted for inhibiting gingipain activity in the brain and are emerging as potential therapeutic agents for mitigating cell damage and disease progression.^22,224

Much like the gut microbiome, the therapeutic use of probiotics has shown effectiveness in maintaining microbial balance in the mouth. Research has demonstrated that oral probiotics have similar effects of promoting microbiota diversity and reducing plaque accumulation as manual disruption of the biofilm through brushing and flossing.^25-26 Several bacterial strains have demonstrated inhibitory effects on pathogen growth, the formation of oral biofilms, and the disruption of pre-formed biofilms, including Lactobacillus,^25-28 Bifidobacterium,²⁶ Streptococcus,^27,28 and Lactococcus.²⁹ A 2021 study found that Streptococcus salivarius is able to adhere to gingival fibroblasts and inhibit inflammatory cytokine IL-6 and IL-8 production in the presence of anaerobic bacteria such as P. gingivalis.³⁰ Bifidobacterium and Lactobacillus were also shown to improve the clinical indicators of periodontitis such as attachment loss and pocket depth and bleeding on probing.²⁸ In addition to their efficacy as antimicrobial agents, the use of these commensal bacteria may also support the integrity of oral tissue and, in turn, is likely to decrease the incidence of bacterial translocation through permeation.

A small 2018 double-blind placebo controlled randomized clinical trial of middle-aged adults tested the total cultivable bacteria of the mouth before and after mechanical plaque removal against treatment with an orally administered probiotic sachet of Lactobacillus rhamnosus.²⁵ At the six and nine-month time points, bacterial cultures in both groups had decreased, with no significant difference in efficacy between the two modalities. Furthermore, other studies suggest that oral probiotics as an adjunctive to daily hygiene habits yield the lowest concentrations of overall pathogenic bacteria.^25,31

Conclusion

Improving oral health may help to minimize risk factors associated with the onset of a range of chronic neurodegenerative conditions, including dementia. Dysbiosis in the oral microbiome may be mitigated by several strategies common to the functional medicine framework, including nutritional approaches and lifestyle changes. Common over-the-counter oral health products containing probiotics such as toothpastes, mints, or lozenges may be cost-effective strategies for improving a patient’s oral health at home. In addition to daily brushing and flossing, increasing dietary intake of probiotics, nitrite-rich foods, and polyphenols can optimize oral microbiota and decrease overall inflammatory burden. Oral hygiene is an important lifestyle factor for patients, and addressing early manifestations of disease originating in the mouth can help maintain proper function and health throughout the body.