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

Deborah K Shoemark, Shelley J Allen

Research output: Contribution to journalArticle (Academic Journal)

84 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)725-38
Number of pages14
JournalJournal of Alzheimer's Disease
Volume43
Issue number3
Early online date13 Aug 2014
DOIs
Publication statusPublished - 2015

Keywords

  • Alzheimer's disease
  • blood-brain barrier
  • environmental
  • epidemiological
  • immune-tolerated
  • innate
  • microbiome
  • oral
  • polymorphism

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