Oral-Gut-Brain Axis in Experimental Models of Periodontitis: Associating Gut Dysbiosis With Neurodegenerative Diseases

Abstract

Periodontitis is considered a non-communicable chronic disease caused by a dysbiotic microbiota, which generates a low-grade systemic inflammation that chronically damages the organism. Several studies have associated periodontitis with other chronic non-communicable diseases, such as cardiovascular or neurodegenerative diseases. Besides, the oral bacteria considered a keystone pathogen, Porphyromonas gingivalis, has been detected in the hippocampus and brain cortex. Likewise, gut microbiota dysbiosis triggers a low-grade systemic inflammation, which also favors the risk for both cardiovascular and neurodegenerative diseases. Recently, the existence of an axis of Oral-Gut communication has been proposed, whose possible involvement in the development of neurodegenerative diseases has not been uncovered yet. The present review aims to compile evidence that the dysbiosis of the oral microbiota triggers changes in the gut microbiota, which creates a higher predisposition for the development of neuroinflammatory or neurodegenerative diseases.The Oral-Gut-Brain axis could be defined based on anatomical communications, where the mouth and the intestine are in constant communication. The oral-brain axis is mainly established from the trigeminal nerve and the gut-brain axis from the vagus nerve. The oral-gut communication is defined from an anatomical relation and the constant swallowing of oral bacteria. The gut-brain communication is more complex and due to bacteria-cells, immune and nervous system interactions. Thus, the gut-brain and oral-brain axis are in a bi-directional relationship. Through the qualitative analysis of the selected papers, we conclude that experimental periodontitis could produce both neurodegenerative pathologies and intestinal dysbiosis, and that periodontitis is likely to induce both conditions simultaneously. The severity of the neurodegenerative disease could depend, at least in part, on the effects of periodontitis in the gut microbiota, which could strengthen the immune response and create an injurious inflammatory and dysbiotic cycle. Thus, dementias would have their onset in dysbiotic phenomena that affect the oral cavity or the intestine. The selected studies allow us to speculate that oral-gut-brain communication exists, and bacteria probably get to the brain via trigeminal and vagus nerves.

From Mouth to Brain: Distinct Supragingival Plaque Microbiota Composition in Cerebral Palsy Children With Caries

“…Keeping in mind that bacteria in the oral cavity can be ingested and translocate to other parts of the gastrointestinal tract, the overgrowth of the unwanted bacterial population in the oral cavity poses great risk to human health, potentially triggering a “chain reaction” via disruption of the gut microbiota either via displacing natural inhabitants in the gastrointestinal tract or even killing them via production of harmful toxins. Consequently, the anatomical communication ( Sansores-España et al, 2021 ) between the oral cavity and gut offers a new perspective in the well-established gut–brain axis that is associated with neuroinflammation, neurodegenerative diseases (e.g., impaired motor function or dementia), and neuropsychiatric disorders (e.g., depression, anxiety, bipolar disorder) ( Kelly et al., 2015 ; Lee et al., 2018 ; Mohajeri et al., 2018 ; Lee et al., 2019 ; Parker et al., 2020 ), specifically on how microbes in the oral cavity take part in the development of neurological/neurodegenerative disease via the oral–gut–brain axis. For the case of dental caries, a recently published scoping review ( Latti et al., 2018 ) indicated the lack of evidence from human studies to clearly explain the association of dental caries ( Ferreira et al., 2021a ) and systemic diseases, which constitutes a research gap ( Wu et al., 2016 ; Maitre et al., 2020 ; Orr et al., 2020 ).…”

The Antimicrobial Properties of Cannabis and Cannabis-Derived Compounds and Relevance to CB2-Targeted Neurodegenerative Therapeutics

“…It must be recognized that a potential microbial etiology for neurodegenerative diseases has been postulated for some time, with the oral and gut microbiota particularly implicated, as reviewed extensively elsewhere [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. This has fostered the possibility of the development of suitable bacteria-targeted therapeutic strategies, some of which show promise in animal models [ 80 , 81 , 84 , 85 , 86 ].…”

“…It remains to be clarified if it is a general dysbiosis, specific bacteria and their virulence factors, or both that may be most important in the development of Parkinson’s disease, Alzheimer’s disease and other neuropathologies. In addition to direct mechanisms, etiological roles for bacterial-induced inflammation and an irregular microbial metabolome have also been posited [ 75 , 76 , 78 , 79 , 80 ]. Therefore, the unintended consequences of CB2-agonists with antimicrobial properties may be hard to predict.…”

Porphyromonas gingivalis Conditioned Medium Induces Amyloidogenic Processing of the Amyloid-β Protein Precursor upon in vitro Infection of SH-SY5Y Cells

“…P. gingivalis has also been implicated in the instigation of inflammatory mediator (cytokines) release locally, which may lead to systemic spread via circulating blood [5,6]. Hence, P. gingivalis attains greater significance not only in periodontitis but also as an initiator for pro-inflammatory cytokines (IL-1␤, IL-6, and others) [7], which has been shown to contribute to the development of multiple systemic diseases including cardiovascular disease, hyperglycemia, and insulin resistance [8][9][10][11][12][13][14]. Periodontitis is a chronic condition, and its effective management requires frequent chairside periodontal therapy with patient's adherence to oral hygiene and professional compliance.…”