State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, China.
Phytomedicine. 2020 Feb;67:153157. doi: 10.1016/j.phymed.2019.153157. Epub 2019 Dec 23.
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.
Therefore, the microbiota-gut-brain axis was used to investigate the antidepressive properties of FOSs at the interface of the gut microbiota (GM).
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.
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 HS, that exhibit antidepressant-like 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.
In conclusion, this study implied that antidepressant efficacy of FOSs was inseparable from and strongly associated with the modulation of the host' s GM.
从巴戟天中提取的菊粉型低聚果糖(FOS)是一种有效的治疗轻中度抑郁症的口服抗抑郁药,但它的疗效和生物利用度还知之甚少。
因此,本研究从肠道微生物群(GM)的角度利用微生物群-肠道-大脑轴来研究 FOS 的抗抑郁特性。
通过胃内灌胃将 FOS 引入到慢性不可预测轻度应激(CUMS)的大鼠中,并通过行为测试、肠道形态和皮质酮水平来研究其抗抑郁作用。从粪便中提取细菌基因组 DNA,采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 GM 进行分析。
FOS 缓解了抑郁样行为并修复了肠道上皮损伤。FOS 治疗降低了模型大鼠血浆和尿液中的皮质酮水平。此外,正常和模型大鼠的 GM 组成明显聚类,主要与有益细菌(如不动杆菌属、Barnesiella、粪球菌属、粪杆菌属、乳杆菌属和芽孢杆菌属)的消失和与抑郁相关的细菌(如厌氧棒状杆菌属、 Oscillibacter、变形菌门和链球菌属)的出现有关。有趣的是,FOS 治疗恢复了抑郁大鼠肠道的菌群失调。值得注意的是,FOS 促进了蓝细菌门的细菌丰度增加,蓝细菌门是一群已知分泌具有药理重要性代谢物的细菌,如 HS,具有抗抑郁样特性。显然,与 FOS 的一个成分(聚合度 5)和抗抑郁标准药物氟西汀相比,FOS 诱导的 GM 调节具有更强的抗抑郁作用。
总之,本研究表明,FOS 的抗抑郁作用与宿主 GM 的调节密不可分且密切相关。