Chronic ethanol exposure induced anxiety-like behaviour by altering gut microbiota and GABA system

Ethanol, also known as alcohol, is one of the most common drinks in the world. Chronic ethanol exposure has been reported to induce mental disorders. Ethanol also has a strong effect on the gut microbiota. The gut microbiota has been reported to affect the brain via multiple pathways, including changes in γ-aminobutyric acid (GABA) system, and cause a variety of mental disorders. The GABA system in the cortex is associated with anxiety. However, the role of gut microbiota played in ethanol exposure-induced changes in the GABA system and anxiety is still not clear. We established a 30-day ethanol exposure mouse model and investigated the effects of microbiota using the antibiotic minocycline. Minocycline alleviated ethanol-induced anxiety-like behaviour, dysbiosis of microbiota, intestinal barrier disruption, increased serum endotoxin and interleukin (IL)-6. Minocycline also attenuated ethanol-induced apoptosis and decreased expression of glutamate decarboxylases (GADs) and GABRA1 in the prefrontal cortex. Our results indicated that gut microbiota plays an important role in ethanol-induced anxiety-like behaviour by altering the function of GABA system. In addition, causal mediation analysis showed that endotoxin and IL-6 may mediate the connection between the gut microbiota and the expression of GABA_A receptor in the prefrontal cortex.