Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, China.
Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Pharmacol Res. 2021 Mar;165:105439. doi: 10.1016/j.phrs.2021.105439. Epub 2021 Jan 22.
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.
肠道微生物群被认为是治疗焦虑症的有前途的治疗靶点。小檗碱（BBR）通过调节肠道微生物群，已显示出在治疗绝经后骨质疏松症、肥胖症和 2 型糖尿病等疾病方面的疗效。然而，BBR 对绝经后焦虑症的影响尚不清楚。本研究旨在测试 BBR 是否通过在雌激素缺乏条件下调节肠道微生物群来改善焦虑症。在特定病原体自由（SPF）去卵巢（OVX）大鼠中建立实验性焦虑症，然后用 BBR 治疗 4 周，再进行行为测试。旷场和高架十字迷宫测试表明，与 vehicle 处理组相比，BBR 治疗显著改善了 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，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、乳杆菌和阿克曼氏菌，并表现出更高的雌马酚生成。值得注意的是，BBR 灌胃对接受卵巢切除术的无菌（GF）大鼠没有明显的抗焦虑作用，而来自 SPF 大鼠的粪便微生物群移植的 GF 大鼠在焦虑样症状和异黄酮水平方面与供体大鼠显著相似。本研究表明，肠道微生物群在治疗卵巢切除术后加重的焦虑症中至关重要，BBR 对肠道微生物群的调节是治疗绝经后焦虑症的一种有前途的治疗策略。
