such as LPS and 16S DNA, activating innate immune signaling and increasing circulating cytokines like TNF-α and IL-6 (Bala et al., 2014; Leclercq et al., 2012). In individuals with an alcohol use disorder, however, endotoxin levels increase > 5-fold compared with healthy controls, leading to increased peripheral inflammatory responses (Parlesak et al., 2000). Excessive drinkers have higher levels of serum LPS and other markers of immune activation that correlate with the quantity of alcohol consumed, and levels of these markers decrease after abstinence (Girard et al., 2017; Liangpunsakul et al., 2017). Acting as a powerful driver of TLR4 signaling, circulating LPS activates hepatic Kupffer cells to produce inflammatory cytokines and chemokines, which contribute to alcohol-induced liver injury (Roh and Seki, 2013). Alcohol also induces miR-155 and HDAC11 expression, which inhibits negative regulators of the TLR4 pathway and increases LPS responsiveness of mouse Kupffer cells (Bala et al., 2017). In addition to the liver, the gut wall or adipose tissue also contribute to systemic inflammation in AUD (de Timary et al., 2017). Similar findings have been observed in nonhuman primate models of AUD. In primates exposed to chronic ethanol, changes in immune homeostasis in peripheral blood and intestinal mucosa may be
