Future studies aimed at uncovering the mechanisms underlying dose-dependent modulation of immune function should also investigate changes in gene expression patterns, as well as factors that regulate gene expression including microRNAs and epigenetic changes within specific immune cell populations. Additionally, the role of alcohol-induced changes in the microbiome on immunity should be studied. Recent studies have shown that the microbiome modulates immunity in the gut, and in turn, immunity modulates the microbiome in the gut (Belkaid and Hand 2014). Only two studies have examined alcohol-induced changes in colonic (Mutlu, Gillevet et al. 2012) and fecal microbiomes (Chen, Yang et al. 2011), and both studies focused on individuals with AUD. Finally, an emerging informatics approach that can piece together these extensive data sets and build a network between the immune response elements, the HPA axis, and the time-course/dose response of ethanol while emphasizing in vivo studies from rodent, non human primate, and humans is urgently required.
