Prevotella histicola Mitigated Estrogen Deficiency-Induced Depression via Gut Microbiota-Dependent Modulation of Inflammation in Ovariectomized Mice.

Prevotella histicola Mitigated Estrogen Deficiency-Induced Depression via Gut Microbiota-Dependent Modulation of Inflammation in Ovariectomized Mice.
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DOI:
10.3389/fnut.2021.805465
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发表时间:
2021
影响因子:
5
通讯作者:
Wang F
Wang F
中科院分区:
农林科学2区
文献类型:
--
作者:
Huang F;Liu X;Xu S;Hu S;Wang S;Shi D;Wang K;Wang Z;Lin Q;Li S;Zhao S;Jin K;Wang C;Chen L;Wang F

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雌激素缺乏引起的抑郁症与肠道菌群失衡和炎症密切相关。组织普氏菌 (P. histicola) 是一种新兴的益生菌,可明显改善炎症反应。本研究旨在验证 P. histicola 的抗抑郁样作用并阐明其潜在机制。小鼠接受 P. histicola 治疗,并在卵巢切除术 (OVX) 后同养。通过行为任务检查小鼠抑郁样行为的变化,并通过 16S rRNA 测序检测微生物群的变化。通过H&E、尼氏染色、qRT-PCR、蛋白质印迹和免疫荧光观察神经元损伤、蛋白质合成、炎症因子、肠道通透性和神经增殖的变化。 P. histicola 可显着减少雌激素缺乏引起的抑郁样行为和神经元损伤。此外,P. histicola 显着增加了肠道菌群的丰度,尤其是乳杆菌和阿克曼氏菌。同时,与OVX小鼠相比,共养小鼠也具有更好的情绪状态和中性结构。还发现 P. histicola 上调回肠和结肠中的紧密连接蛋白 ZO-1、occludin、claudin-1 和 MUC2,降低主要在回肠和结肠中的炎症因子 VCAM、MCP-1、IL-6、IL-8 和 TNF-α 的水平,并降低 COX-2、TLR4、Myd88、JNK、MCP-1、IL-6、IL-8 和海马体中的 TNF-α。此外,在 P. histicola 处理后观察到细胞凋亡(caspase-3 和 caspase-8)显着下调和神经营养因子(BDNF 和 Ki-67)上调。我们的数据表明,P. histicola 通过改善肠道微生物群、修复肠漏、抑制中枢炎症、促进海马神经发生中 BDNF 的表达,显着减轻 OVX 小鼠的抑郁症。 P. histicola 可能对 PMD 有治疗作用。
Estrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation. Prevotella histicola (P. histicola), an emerging probiotic, apparently improves inflammatory responses. This study aims to verify the antidepressant-like effects of P. histicola and clarify its potential mechanisms. Mice were treated with P. histicola and cohousing after ovariectomy (OVX). The changes in depression-like behaviors among mice were examined by behavioral tasks, and alterations in the microbiota were detected through 16S rRNA sequencing. Changes in neuronal injury, protein synthesis, inflammatory factors, intestinal permeability, and nerve proliferation were observed by H&E, Nissl staining, qRT-PCR, western blotting, and immunofluorescence. P. histicola significantly reduces depression-like behaviors and neuronal damage induced by estrogen deficiency. Additionally, P. histicola significantly increases the abundance of intestinal flora, especially Lactobacillus and Akkermansia. Meanwhile, the cohoused mice also had a better emotional state and neutral structure compared with OVX mice. P. histicola was also found to upregulate tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the ileum and colon and reduce the levels of inflammatory factors VCAM, MCP-1, IL-6, IL-8, and TNF-α, mainly in the ileum, colon, and decrease the expression of COX-2, TLR4, Myd88, JNK, MCP-1, IL-6, IL-8, and TNF-α in the hippocampus. Moreover, significant downregulation of apoptosis (caspase-3 and caspase-8) and upregulation of neurotrophic factors (BDNF and Ki-67) were observed after P. histicola treatment. Our data show that P. histicola significantly mitigates depression of OVX mice through improvement in intestinal microbiota to repair intestinal leakage and inhibit central inflammation to promote the expression of BDNF for hippocampal neurogenesis. P. histicola may be therapeutically beneficial for PMD.
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