RESUMO
The epidemic of alcohol abuse affects millions of people worldwide. Relevant evidence supports the notion that the gut microbiota (GM) plays a crucial role in central nervous system (CNS) function, and its composition undergoes changes following alcohol consumption. Therefore, the purpose of this study was to investigate the effect of reconstructing the gut microbiota by fecal microbiota transplantation (FMT) on alcohol dependence. Here, we established an alcohol dependence model with C57BL/6J mice and proved that FMT treatment improved anxiety-like behavior and alcohol-seeking behavior in alcohol-dependent mice. Additionally, we found that the expression of the intestinal intercellular tight junction structure proteins ZO-1 and occludin was significantly increased after FMT. FMT repaired intestinal permeability in alcohol-dependent mice and decreased the levels of lipopolysaccharide (LPS) and proinflammatory factors. Moreover, the serotonin (5-hydroxytryptamine, 5-HT) content was significantly increased in alcohol-dependent mouse intestinal and brain tissues after receiving the fecal microbiome from healthy mice. 16S rRNA sequencing demonstrated that FMT markedly reshaped the composition of the gut microbiota and elicited changes in the intestinal barrier and 5-HT levels. Collectively, our results revealed that FMT has a palliative effect on alcohol dependence and explored the underlying mechanisms, which provides new strategies for the treatment of alcohol dependence.
RESUMO
Accumulating evidence points to a critical role of the brain gut axis as an important paradigm for many central nervous system diseases. Recent studies suggest that propolis has obvious neuroprotective properties and functionality in regulating intestinal bacteria flora, hinting at a potential key effect at both terminals of this axis regulation. However, currently no clear evidence confirms the effects of propolis on alcohol-induced depression. Here, we establish an alcoholic depression model with C57BL/6J mice and demonstrate that treatment with propolis protects against alcohol-induced depressive symptoms by behavioral tests. In addition, propolis attenuates the injury of nerve cells in the hippocampal region and restores the serum levels of brain-derived neurotrophic factor (BDNF) and dopamine (DA) in mice with alcohol-induced depression. Pathology and biotin tracer assays show that propolis repairs the intestinal leakage caused by alcohol. Additionally, propolis treatment increases the expression levels of intestinal intercellular tight junctions' (TJs') structural proteins Claudin-1, Occludin and zona occludens-1 (ZO-1), as well as the activation state of the liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) signaling pathway, which is closely related to the intestinal permeability. Furthermore, propolis can reduce the levels of pro-inflammatory, lipopolysaccharide (LPS) and fatty-acid-binding protein 2 (FABP2), suggesting the significance of the inflammatory response in alcoholic depression. Collectively, our findings indicate that propolis exerted an improving effect on alcohol-induced depressive symptoms by ameliorating brain gut dysfunction.