Gut microbiota modulates depressive-like behaviors induced by chronic ethanol exposure through short-chain fatty acids

作者：Hui Shen, Chaoxu Zhang, Qian Zhang, Qing Fang Lv, Hao Liu, Huiya Yuan, Changliang Wang, Fanyue Meng, Yufu Guo, Jiaxin Pei, Chenyang Yu, Jinming Tie, Xiaohuan Chen, Hao Yu, Guohua Zhang, Xiaolong Wang · 发表于：Journal of Neuroinflammation · 年份：2024 · DOI：10.1186/s12974-024-03282-6 · 被引用次数：55 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Alcohol Consumption and Health Effects

BACKGROUND: Chronic ethanol exposure (CEE) is recognized as an important risk factor for depression, and the gut-brain axis has emerged as a key mechanism underlying chronic ethanol exposure-induced anxiety and depression-like behaviors. Short-chain fatty acids (SCFAs), which are the key metabolites generated by gut microbiota from insoluble dietary fiber, exert protective roles on the central nervous system, including the reduction of neuroinflammation. However, the link between gut microbial disturbances caused by chronic ethanol exposure, production of SCFAs, and anxiety and depression-like behaviors remains unclear. METHODS: Initially, a 90-day chronic ethanol exposure model was established, followed by fecal microbiota transplantation model, which was supplemented with SCFAs via gavage. Anxiety and depression-like behaviors were determined by open field test, forced swim test, and elevated plus-maze. Serum and intestinal SCFAs levels were quantified using GC-MS. Changes in related indicators, including the intestinal barrier, intestinal inflammation, neuroinflammation, neurotrophy, and nerve damage, were detected using Western blotting, immunofluorescence, and Nissl staining. RESULTS: Chronic ethanol exposure disrupted with gut microbial homeostasis, reduced the production of SCFAs, and led to anxiety and depression-like behaviors. Recipient mice transplanted with fecal microbiota that had been affected by chronic ethanol exposure exhibited impaired intestinal structure ...