AUTHOR BLOCK: *P. PUJOLS, K. RIVERA, A. GHEZZI, I. RODRÍGUEZ-FERNÁDEZ;
Univ. of Puerto Rico, Rio Piedras, San Juan, PR

Abstract:

Introduction:
Alcohol Use Disorder (AUD) is a medical condition characterized by a limited ability to stop or control alcohol use despite adverse social, occupational, or health consequences. In older adults, the habit of excessive alcohol consumption represents 20% between the ages 60 to 64 years and 11% over 65 years of age, according to the National Survey and Drug Use and Health. Aging can affect the response to alcohol in aspects of sensitivity and tolerance, which puts the elderly at greater risk. Thus, there is an urgent need to characterize the cellular and molecular effects of alcohol consumption in this aging population. Aging has twelve proposed hallmarks but of particular interest for our project is the altered intercellular communication between the animal genome and the microbiome leading to microbial dysbiosis. The human being is home to around 38 trillion bacteria and this collective commensal, symbiotic, and pathogenic microorganisms is known as the microbiota, the majority of which is found in the intestine.

Methods:

Our study aims to understand the effects of alcohol on the bidirectional interaction of the gut microbiome and the brain in aspects of tolerance and sensitivity in young and old animals. We are using Drosophila melanogaster as a model organism as it has homology with humans in alcohol response, intestinal microbiome composition, and displays aging phenotypes. To measure age-related changes in alcohol behaviors, we exposed young (7 days) and old (45 days) Canton-S female flies to 50% ethanol vapor. We then calculated the time they take to sedate. For sensitivity assays, we measured resistance to alcohol in a first exposure compared to a control group that is exposed to water. While for tolerance we calculated the difference between resistance from a second exposure generated by a previous one. We then measure the changes in the gut microbiome after one or two exposures to alcohol. To do this we dissected the intestine of treated flies and plated the homogenate in selective media for Lactobacilli, Acetobacteria, and Enterobacteria and measure abundance in Colony Forming Units (CFUs).

Results:

Our data shows that there is an increase in sensitivity and tolerance in old flies. In young and old flies, we find that after one exposure to alcohol, all CFUs increase and then decrease during the second exposure. Young flies treated with antibiotics have a decrease in tolerance.

Conclusions:

Future studies are focused on finding the molecular mechanism used by specific bacterial species to influence sensitivity and tolerance in flies. We hope to elucidate the underlying causes of neuroadaptation possibly caused by changes in the gut microbiome and to further understand these changes in the aging context.