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

Abstract

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 GABAA receptor in the prefrontal cortex.

Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation

“…The minimal sample size was pre-determined by the nature of experiments. No statistical methods were used to pre-determine sample sizes, but our sample sizes are similar to those reported in previous publications [ 4 , 27 ]. Details of the number of independent experiments are provided in the figure legends.…”

“…Causal mediation analysis was used to explore the mediation effect of inflammatory cytokines on the association between the gut microbiota and depressive-like behavior [ 26 , 27 ]. We applied the Z score to quantify the performance of mice that received FMTs from NLRP3-shRNA groups in behavioral tests.…”

Antibiotic-induced gut dysbiosis and cognitive, emotional, and behavioral changes in rodents: a systematic review and meta-analysis

“…It should also be noted that not all antibiotics have a potentially depressogenic effect. For example, minocycline (a broad-spectrum antibiotic) was used in one of the experiments to test its anxiolytic effect ( Yao et al, 2022 ).…”

Comparison of LPS and MS-induced depressive mouse model: behavior, inflammation and biochemical changes

“…After completing the behavior tests, mice were anesthetized with isoflurane, and blood from portal vein and vena cava was centrifuged as previously reported [ 27 ] and serum samples were stored in a − 80 °C freezer. Mice were then decapitated after cervical dislocation.…”