The Microbiome and Disease: Reviewing the Links between the Oral Microbiome, Aging, and Alzheimer's Disease

Abstract

This review, gathered from diverse sources, shows how our microbiome influences health and ultimately how well we age. Evidence linking oral bacteria to Alzheimer's disease (AD) is discussed in the context of aging, drawing together data from epidemiological, experimental, genetic, and environmental studies. Immunosenescence results in increased bacterial load as cell-mediated and humoral immune responses wane. The innate immune system gradually takes over; contributing to the rise in circulating proinflammatory cytokines such as TNFα. Maintaining the integrity of the blood-brain barrier (BBB) against a backdrop of increasing bacterial load is important. Aging may favor the proliferation of anaerobes in the mouth eliciting a robust TNFα response from the oral epithelium. Prolonged exposure to high levels of circulating TNFα compromises the integrity of the BBB. Sensitive techniques now detect the "asymptomatic" presence of bacteria in areas previously thought to be sterile, providing new insights into the wider distribution of components of the microbiome. These "immune-tolerated" bacteria may slowly multiply elsewhere until they elicit a chronic inflammatory response; some are now considered causal in instances of atherosclerosis and back pain. Inflammatory processes have long been associated with AD. We propose for a subset of AD patients, aging favors the overgrowth of oral anaerobes established earlier in life provoking a pro-inflammatory innate response that weakens the BBB allowing bacteria to spread and quietly influence the pathogenesis of AD. Finally, we suggest that human polymorphisms considered alongside components of the microbiome may provide new avenues of research for the prevention and treatment of disease.

Can Better Management of Periodontal Disease Delay the Onset and Progression of Alzheimer’s Disease?

“…Oral bacteria are associated with diverse pathologies, which are often co-morbid with AD ( Fig. 1) as described elsewhere [28]. As periodontitis is an easily manageable risk factor for a number of conditions, we argue that reducing the incidence of periodontal disease is a preventative measure for numerous health benefits in later life.…”

“…Nutritional deficiency also correlates with cognitive decline [71], and fewer teeth may lead an individual reducing their intake of fresh foods, which in turn may decrease intake of B-vitamins and folic acid and other 8 forms of nutrition [28]. Taken together, factors causing deterioration in cognition are multifactorial and complex with likely contribution from primary infection and nutritional deficiency due to loss of teeth.…”

Microbiome Disturbances and Autism Spectrum Disorders

“…There are isolated reports detailing the effects that the oral cavity microbiome exerts on neural function. Oral cavity microbial shifts are associated with seizure severity in epileptic patients (Costa et al, 2014) and Alzheimer's disease (Noble et al, 2014;Shaik et al, 2014;Shoemark and Allen, 2015). Vaginal dysbiosis, such as may occur through maternal stress, might affect offspring neurobehavioral development (Ja sarevi c et al, 2015); however, sufficient data to support this claim is currently lacking.…”

Inflammasome Involvement in Alzheimer’s Disease

“…One in six people over 80 years in the UK has dementia (16). Estimates for the prevalence of AD in the USA indicate that more than 5 million individuals who are 65 years or older currently suffer from AD (1,15).…”