Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Dysbiosis in Alzheimer’s Disease Might be Triggered by Certain Classes of Antibiotics with Time-lapse: New Insights in the Pathogenesis?

Version 1 : Received: 22 December 2021 / Approved: 5 January 2022 / Online: 5 January 2022 (10:44:59 CET)

How to cite: Ternák, G.; Németh, M.; Rozanovic, M.; Bogár, L. Dysbiosis in Alzheimer’s Disease Might be Triggered by Certain Classes of Antibiotics with Time-lapse: New Insights in the Pathogenesis? . Preprints 2022, 2022010032 (doi: 10.20944/preprints202201.0032.v1). Ternák, G.; Németh, M.; Rozanovic, M.; Bogár, L. Dysbiosis in Alzheimer’s Disease Might be Triggered by Certain Classes of Antibiotics with Time-lapse: New Insights in the Pathogenesis? . Preprints 2022, 2022010032 (doi: 10.20944/preprints202201.0032.v1).

Abstract

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative illness, responsible for 60-70% of all dementias, affecting over 50 million people worldwide, and nearly 11 million in European countries. Several putative factors are identified in the literature as causative agents or risk factors for the development of AD. The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades. Recent studies raised the possible role of dysbiosis in the development of AD which prevents memory loss. The amyloid-β (Aβ) deposition might be considered as an inflammatory reaction to certain molecular products arising from the altered microbiome. Based on the above observations, it has been suspected, that antibiotic consumption patterns of different antibiotic classes might be associated with the prevalence of AD in European countries. Methods: Antibiotic consumption (ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, have 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 year 1997-2007 (p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-18, 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) (p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (p: 0.063), but none for the years 1997-2007 (p: 0.241). Broad-spectrum, beta-lactamase sensitive penicillin (J01CA) consumption showed a positive (non-significant) correlation with the prevalence of AD for the years 2008-2018 (p:0.080).Discussion: 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

antibiotic consumption; gut flora; dysbiosis; Alzheimer disease; dementia; gut-brain axis, mediator molecules

Subject

MEDICINE & PHARMACOLOGY, Pathology & Pathobiology

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