Alzheimer's Disease-Related Dysbiosis Might Be Triggered by Certain Classes of Antibiotics with Time-Lapse: New Insights into the Pathogenesis?

J Alzheimers Dis. 2022;87(1):443-451. doi: 10.3233/JAD-220018.

Abstract

Background: Several putative factors are identified in the literature as causative agents or risk factors for the development of Alzheimer's disease (AD). The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades, but recent studies raised the possible role of dysbiosis in the development of AD, which prevents memory loss.

Objective: Finding possible associations between antibiotic consumption patterns and the prevalence of AD in European countries.

Methods: Antibiotic consumption (European Centre for Disease Prevention and Control, ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, has been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation.

Results: A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the years 1997-2007 (r: 0.37, p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-2018, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (r: 0.406, p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (r: 0.344, p: 0.063), but none for the years 1997-2007 (r: 0.256, p: 0.241).

Conclusion: Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

Keywords: Alzheimer’s disease; antibiotic consumption; dementia; dysbiosis; gut flora; gut-brain axis; mediator molecules.

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid
  • Anti-Bacterial Agents / adverse effects
  • Dysbiosis / chemically induced
  • Dysbiosis / epidemiology
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Quinolones*
  • Time-Lapse Imaging

Substances

  • Amyloid
  • Anti-Bacterial Agents
  • Quinolones