A meta-analysis of the effect of binge drinking on the oral microbiome and its relation to Alzheimer\u2019s disease

Ayuni Yussof,Paul Yoon,Sarah Schweinberg,Cayley Krkljes,Tinchun Chu,Sulie L Chang,Jessica Cottrell

doi:10.1038/s41598-020-76784-x

Abstract

The diversity of bacterial species in the oral cavity makes it a key site for research. The close proximity of the oral cavity to the brain and the blood brain barrier enhances the interest to study this site. Changes in the oral microbiome are linked to multiple systemic diseases. Alcohol is shown to cause a shift in the microbiome composition. This change, particularly in the oral cavity, may lead to neurological diseases. Alzheimer’s disease (AD) is a common neurodegenerative disorder that may cause irreversible memory loss. This study uses the meta-analysis method to establish the link between binge drinking, the oral microbiome and AD. The QIAGEN Ingenuity Pathway Analysis (IPA) shows that high levels of ethanol in binge drinkers cause a shift in the microbiome that leads to the development of AD through the activation of eIF2, regulation of eIF4 and p70S6K signaling, and mTOR signaling pathways. The pathways associated with both binge drinkers and AD are also analyzed. This study provides a foundation that shows how binge drinking and the oral microbiome dysbiosis lead to permeability changes in the blood brain barrier (BBB), which may eventually result in the pathogenesis of AD.

Highlights

The diversity of bacterial species in the oral cavity makes it a key site for research
One of the leading detection methods to study the oral microbiome is via 16 s ribosomal RNA (16 s rRNA) gene profiling, which is used in this study[33]
This study, on the other hand, looks on two factors that are inter-related in the pathogenesis of Alzheimer’s disease (AD), which are binge drinking and the oral microbiome

Summary

Result

The top pathway is Eukaryotic Initiation Factor 2 (eIF2) with 59 affected, Z-score of 5.477, − log(p value) of 39.747 and p value of 1.79E−40. The double stranded RNA-activated protein kinase or eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2 or PKR) increases inhibition of phosphorylated eIF2α30. The phosphorylation of eIF2α subunits by various kinase such as eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3 or PERK) and EIF2AK2 (PKR). MRNAs that can undergo translation are β-secretase enzyme (BACE1) and the CREB repressor, activating transcription factor 4 (ATF4) Both have been associated with the AD pathology. The decreased level of APOA1 leads to the inhibition of clearance and neutralization of LPS, which is indicated by the blue molecules and the blue arrows This figure exhibits the effects of the alcohol increase and LPS in binge drinkers. The increase in ethanol shows to activate the expression of LPS and the increase of LPS shows the activation of the LPS/IL1 response element and the LPS binding

Discussion

Findings

Materials and methods