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

IF 9.3 1区 医学 Q1 IMMUNOLOGY Journal of Neuroinflammation Pub Date : 2024-11-06 DOI:10.1186/s12974-024-03282-6
Hui Shen, Chaoxu Zhang, Qian Zhang, Qing 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
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Abstract

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 and function, low levels of SCFAs, intestinal inflammation, activation of neuroinflammation, a compromised blood-brain barrier, neurotrophic defects, alterations in the GABA system, anxiety and depression-like behaviors. Notably, the negative effects observed in these recipient mice were significantly alleviated through the supplementation of SCFAs.

Conclusion: SCFAs not only mitigate damage to intestinal structure and function but also alleviate various lesions in the central nervous system, such as neuroinflammation, and reduce anxiety and depression-like behaviors, which were triggered by transplantation with fecal microbiota that had been affected by chronic ethanol exposure, adding more support that SCFAs serve as a bridge between the gut and the brain.

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肠道微生物群通过短链脂肪酸调节慢性乙醇暴露诱发的抑郁样行为
背景:慢性乙醇暴露(CEE)被认为是抑郁症的一个重要风险因素,而肠道-大脑轴是慢性乙醇暴露诱发焦虑和抑郁样行为的一个关键机制。短链脂肪酸(SCFAs)是肠道微生物群由不溶性膳食纤维产生的关键代谢产物,对中枢神经系统具有保护作用,包括减少神经炎症。然而,慢性乙醇暴露引起的肠道微生物紊乱、SCFAs的产生以及焦虑和抑郁样行为之间的联系仍不清楚:方法:首先建立一个为期 90 天的慢性乙醇暴露模型,然后进行粪便微生物群移植模型,通过灌胃补充 SCFAs。焦虑和抑郁样行为通过开阔地试验、强迫游泳试验和高架迷宫来测定。使用气相色谱-质谱对血清和肠道 SCFAs 水平进行量化。利用 Western 印迹、免疫荧光和 Nissl 染色检测了肠道屏障、肠道炎症、神经炎症、神经萎缩和神经损伤等相关指标的变化:结果:慢性乙醇暴露破坏了肠道微生物的平衡,减少了SCFAs的产生,并导致焦虑和抑郁样行为。移植了受慢性乙醇暴露影响的粪便微生物群的受体小鼠表现出肠道结构和功能受损、低水平的 SCFAs、肠道炎症、神经炎症激活、血脑屏障受损、神经营养缺陷、GABA 系统改变、焦虑和抑郁样行为。值得注意的是,通过补充 SCFAs,在这些受体小鼠身上观察到的负面影响得到了显著缓解:SCFAs不仅能减轻肠道结构和功能的损伤,还能减轻中枢神经系统的各种病变,如神经炎症,并减少因移植受慢性乙醇暴露影响的粪便微生物群而引发的焦虑和抑郁样行为。
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来源期刊
Journal of Neuroinflammation
Journal of Neuroinflammation 医学-神经科学
CiteScore
15.90
自引率
3.20%
发文量
276
审稿时长
1 months
期刊介绍: The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes. Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems. The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.
期刊最新文献
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