Berberine ameliorates ovariectomy-induced anxiety-like behaviors by enrichment in equol generating gut microbiota
Berberine ameliorates ovariectomy-induced anxiety-like behaviors by enrichment in equol generating gut microbiota
复制标题
DOI：
10.1016/j.phrs.2021.105439
复制
发表时间：
2021-03-16
影响因子：
9.3
通讯作者：
Duan, Liping
中科院分区：
文献类型：
--
作者：
Fang, Yuan;Zhang, Jindong;Duan, Liping
肠道微生物群被认为是治疗焦虑的一个有希望的靶点。小檗碱（BBR）通过调节肠道微生物群，在治疗绝经后骨质疏松症、肥胖和2型糖尿病等疾病方面显示出疗效。然而，BBR对绝经后焦虑的影响尚不清楚。本研究的目的是测试BBR是否通过调节雌激素缺乏条件下的肠道微生物群来改善焦虑。在特定无病原体（SPF）卵巢切除（OVX）大鼠中建立实验性焦虑，然后用BBR治疗4周，然后进行行为测试。开放场和升高加迷宫实验表明，与载具处理相比，BBR处理显著改善了OVX大鼠的焦虑样行为。此外，16S rRNA测序和液相色谱/质谱（LC/MS）分析表明，经bbr处理的OVX大鼠具有更高丰度的有益肠道微生物，如拟杆菌、双歧杆菌、乳杆菌和Akkermansia，并显示出增加的马酚生成。值得注意的是，灌喂BBR对切除卵巢的无菌大鼠没有明显的抗焦虑作用，而移植了SPF大鼠粪便微生物群的无菌大鼠在焦虑样症状和异黄酮水平方面与供体大鼠基本相似。该研究表明，肠道微生物群在治疗卵巢切除术加重的焦虑中至关重要，而肠道微生物群的BBR调节是治疗绝经后焦虑症状的一种有希望的治疗策略。
The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal osteoporosis, obesity, and type 2 diabetes through regulating the gut microbiota. However, the effects of BBR on postmenopausal anxiety are still unclear. The purpose of the study is to test whether BBR ameliorates anxiety by modulating intestinal microbiota under estrogen-deficient conditions. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks before undergoing behavioral tests. Open field and elevated plus maze tests demonstrated that BBR treatment significantly ameliorated anxiety-like behaviors of OVX rats compared with vehicle-treated counterparts. Moreover, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis, BBR-treated OVX rats harbored a higher abundance of beneficial gut microbes, such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia, and exhibited increased equol generation. Notably, gavage feeding of BBR had no significant anti-anxiety effects on germ-free (GF) rats that underwent ovariectomy, whereas GF rats transplanted with fecal microbiota from SPF rats substantially phenocopied the donor rats in terms of anxiety-like symptoms and isoflavone levels. This study indicates that the gut microbiota is critical in the treatment of ovariectomy-aggravated anxiety, and that BBR modulation of the gut microbiota is a promising therapeutic strategy for treating postmenopausal symptoms of anxiety.