Fructo-oligosaccharides from Morinda officinalis remodeled gut microbiota and alleviated depression features in a stress rat model
Fructo-oligosaccharides from Morinda officinalis remodeled gut microbiota and alleviated depression features in a stress rat model
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DOI：
10.1016/j.phymed.2019.153157
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发表时间：
2020-02-01
期刊：
影响因子：
7.9
通讯作者：
Zheng, Ying
中科院分区：
文献类型：
--
作者：
Chi, Liandi;Khan, Imran;Zheng, Ying
背景:从巴戟天中纯化出菊粉型低聚果糖。是一种治疗轻度至中度抑郁症的有效口服抗抑郁药，其疗效尚不清楚，生物利用度也很差。目的：因此，采用微生物-肠-脑轴研究FOSs在肠道微生物群（GM）界面的抗抑郁特性。研究设计与方法：采用慢性不可预测轻度应激（CUMS）大鼠灌胃的方式引入FOSs，通过行为学、肠道形态学和皮质酮水平观察其抗抑郁作用。从粪便中提取细菌基因组DNA，并利用肠杆菌重复基因间一致性（ERIC） PCR分析、偏最小二乘判别分析（PLS-DA）和16S rRNA基因焦磷酸测序对基因进行分析。结果：观察到FOSs减轻抑郁样行为，修复肠上皮损伤。FOSs治疗降低了模型大鼠血浆和尿液中的皮质酮水平。此外，正常大鼠和模型大鼠的转基因成分分布较远，主要与抑郁大鼠有益菌（如不动杆菌、巴氏杆菌、粪球菌、Dialister、乳杆菌和Paenibacillus）的消失和抑郁相关菌（如厌氧杆菌、Oscillibacter、变形杆菌和链球菌）的出现有关。有趣的是，FOSs治疗可以恢复抑郁大鼠肠道的生态失调。值得注意的是，FOSs促进了细菌门蓝藻的丰度，这是一组以分泌药理上重要的代谢物（如H2S）而闻名的细菌，具有抗抑郁的特性。显然，与FOSs的一种成分、聚合度（DP） 5和标准抗抑郁药物氟西汀相比，FOSs诱导的GM调节更具有抗抑郁作用。结论：本研究提示FOSs的抗抑郁作用与宿主GM的调节密不可分，并与之密切相关。
Background: Inulin-type fructo-oligosaccharides (FOSs) purified from Morinda officinalis How., an effective oral antidepressant for mild to moderate depression, have a largely unknown efficacy and poor bioavailability.Purpose: Therefore, the microbiota-gut-brain axis was used to investigate the antidepressive properties of FOSs at the interface of the gut microbiota (GM).Study design and methods: FOSs was introduced via intragastric gavage to rats exposed to chronic unpredictable mild stress (CUMS), and the antidepressive effects were investigated through behavioral tests, intestinal morphology and corticosterone levels. Bacterial genomic DNA was extracted from feces, and the GM was profiled for using enterobacterial repetitive intergenic consensus (ERIC) PCR analysis, partial least squares-discriminant analysis (PLS-DA) and 16S rRNA gene pyrosequencing.Results: It was observed that FOSs alleviated depression-like behaviors and repaired intestinal epithelia damages. FOSs treatment lowered corticosterone levels in the plasma and urine of the model rats. Moreover, the GM compositions of normal and model rats were distantly clustered and were mainly related to the disappearance of beneficial bacteria (e.g., Acinetobacter, Barnesiella, Coprococcus, Dialister, Lactobacillus, and Paenibacillus) and appearance of depression-associated bacteria (e.g., Anaerostipes, Oscillibacter, Proteobacteria, and Streptococcus) in depressive rats. Interestingly, the dysbiosis in depressive rats' gut was reinstated with FOSs treatments. Notably, FOSs promoted the abundance of the bacterial phylum Cyanobacteria, a group of bacteria known for the secretion of pharmacologically important metabolites, such as H2S, that exhibit antidepressantlike properties. Apparently, FOSs-induced modulation of GM was more antidepressive compared to a component of FOSs, degrees of polymerization (DP) 5, and fluoxetine, the standard antidepressant drug.Conclusion: In conclusion, this study implied that antidepressant efficacy of FOSs was inseparable from and strongly associated with the modulation of the host' s GM.