Cyclic Nucleotide Phosphodiesterases in Alcohol Use Disorders: Involving Gut Microbiota

Abstract

Alcohol abuse is one of the most significant public health problems. Chronic, excessive alcohol consumption not only causes alcohol use disorder (AUD), but also changes the gut/lung microbiota, including bacterial and non-bacterial types. Both types of microbiota can release toxins, further damage the gastrointestinal/respiratory tracts, cause inflammation, and impair the functions of the liver, lung and brain, which in turn deteriorates AUD. Phosphodiesterases (PDEs) are critical in the control of intracellular cyclic nucleotides, including cyclic AMP (cAMP) and cyclic GMP (cGMP). Inhibition of certain host PDEs reduces alcohol consumption and attenuates alcohol-related impairment. PDEs are also expressed in the microbiota and may play a potential role in controlling microbiota-associated inflammation. Here, we first summarize the influences of alcohol on gut/lung bacterial and non-bacterial microbiota, as well as on the gut-liver/brain/lung axis. We then discuss the relationship between gut/lung microbiota-mediated PDE signaling and AUD consequences, in addition to highlighting PDEs as potential targets for treatment of AUD.