Unlocking Modifiable Risk Factors for Alzheimer’s Disease: Does the Oral Microbiome Hold Some of the Keys?

Abstract

Advancing age is recognized as the primary risk factor for Alzheimer’s disease (AD); however approximately one third of dementia cases are attributable to modifiable risk factors such as hypertension, diabetes, smoking, and obesity. Recent research also implicates oral health and the oral microbiome in AD risk and pathophysiology. The oral microbiome contributes to the cerebrovascular and neurodegenerative pathology of AD via the inflammatory, vascular, neurotoxic, and oxidative stress pathways of known modifiable risk factors. This review proposes a conceptual framework that integrates the emerging evidence regarding the oral microbiome with established modifiable risk factors. There are numerous mechanisms by which the oral microbiome may interact with AD pathophysiology. Microbiota have immunomodulatory functions, including the activation of systemic pro-inflammatory cytokines. This inflammation can affect the integrity of the blood-brain barrier, which in turn modulates translocation of bacteria and their metabolites to brain parenchyma. Amyloid-β is an antimicrobial peptide, a feature which may in part explain its accumulation. There are microbial interactions with cardiovascular health, glucose tolerance, physical activity, and sleep, suggesting that these modifiable lifestyle risk factors of dementia may have microbial contributors. There is mounting evidence to suggest the relevance of oral health practices and the microbiome to AD. The conceptual framework presented here additionally demonstrates the potential for the oral microbiome to comprise a mechanistic intermediary between some lifestyle risk factors and AD pathophysiology. Future clinical studies may identify specific oral microbial targets and the optimum oral health practices to reduce dementia risk.

The salivary microbiota of patients with acute lower respiratory tract infection–A multicenter cohort study

“…A final possibility is that there may be a bi-directional relationship between LRTI and dysbiosis. Of note, salivary and oral microbiota dysbiosis have been found associated with not only respiratory disorders [ 33 ], but also multiple systemic disorders [ 34 ], including head and neck cancer [ 35 ], autoimmune disorders [ 36 ], and Alzheimer’s disease [ 37 ], and these relationships continue to be explored. With further study on greater numbers of individuals over extended periods of time, it may be possible to establish the presence of gut microbiota in saliva as a marker of respiratory disorders [ 38 ].…”

Characterization and functional prediction of the dental plaque microbiome in patients with alveolar clefts

“…Integral dysbiosis, an imbalance in the makeup of the microbiota, is intimately associated with the onset of certain diseases and significantly undermines overall well-being (Solbiati and Frias-Lopez, 2018). In the interim, modifications in the composition of the oral microbiota have been documented in numerous disorders, including heart failure (Yuzefpolskaya et al, 2023), cardiovascular disease (Altamura et al, 2023), Alzheimer's disease (Loughman et al, 2023), oral cancer (Pispero et al, 2022), type 2 diabetes (Guo et al, 2023), rheumatoid arthritis (Afrasiabi et al, 2023), and systemic lupus erythematosus (Graves et al, 2019). Therefore, it is imperative to investigate the modifications that environmental variables and pathogens produce in oral microbiota.…”

Comparison of Frailty and Chronological Age as Determinants of the Murine Gut Microbiota in an Alzheimer’s Disease Mouse Model

“…In recent years, research in neurodegenerative diseases has focused on the potential influence of the microbiota, mainly within the gut (reviewed in [15,16]). The gut microbiota has been shown to be associated with frailty: faecal samples from frail people had, for example, higher levels of Akkermansia, and lower levels of the genera Faecalibacterium, Prevotella, Roseburia, and Blautia [17].…”