Role of the brain-gut axis in alcohol-related gastrointestinal diseases--what can we learn from new animal models?

Abstract

Ethanol exerts multiple actions on nearly all organs of the body, especially on the central nervous system and the gastrointestinal tract. However, little is known about the effects ethanol has on the brain-gut axis, the linkage between the central neural system and the autonomous innervation of the gastrointestinal tract. It is indisputable that ethanol consumption does affect e.g. exocrine pancreatic secretion or intestinal motility, but it is poorly understood, how alcohol consumption may disturb the brain-gut axis and how this may cause damage to gastrointestinal organs. Due to difficulties in directly assessing ethanol effects on the brain-gut axis in humans, animal models represent a versatile tool to study this topic. However, conventional animal models widely utilized in alcohol research, e.g. the Tsukamoto-French model or the Lieber-DeCarli model, do not mimic the human conditions of ethanol consumption and are therefore not suitable for studies of the brain-gut axis. Established models from other alcohol research disciplines, e.g. addiction research, are by far more applicable. Due to this reason, we have established an animal model of alcohol-dependent rats for the use in gastrointestinal alcohol research. In this model, rats are given free access to different of alcohol solutions (5% and 20% v/v) and tap water. Over time, the rats develop signs of alcohol dependence as seen in humans (e.g. deprivation effect). Organs isolated from rats exposed to this model are currently investigated in our laboratory for alcohol-related gene-regulation compared to non-alcoholic littermates. In addition, non-alcoholic components of alcoholic beverages might affect the brain-gut axis or possibly potentiate the toxicity of ethanol. In our model, commonly ingested alcoholic beverages such as beer, wine, cognac, vodka, and whisky and their non-alcoholic constituents will be tested in future animal studies.