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肠道微生物群与代谢组学相结合揭示了β-环糊精对小鼠的重复剂量口服毒性。

Gut Microbiota Combined With Metabolomics Reveals the Repeated Dose Oral Toxicity of β-Cyclodextrin in Mice.

作者信息

Lv Shuangyu, Zhang Xiaomei, Feng Yu, Jiang Qiying, Niu Chenguang, Yang Yanjie, Wang Xinchun

机构信息

Institute of Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, China.

Key Laboratory of Clinical Resources Translation, The First Affiliated Hospital of Henan University, Kaifeng, China.

出版信息

Front Pharmacol. 2021 Jan 14;11:574607. doi: 10.3389/fphar.2020.574607. eCollection 2020.

DOI:10.3389/fphar.2020.574607
PMID:33519440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7845417/
Abstract

Βeta-cyclodextrin (β-CD) with a hydrophobic cavity enables the formation of inclusion complexes with organic molecules. The formation of host-guest complexes makes the application of β-CD popular in many fields, but their interaction with organisms is poorly understood. In the present study, the effect of β-CD on gut microbiota (16S rRNA gene sequencing), serum metabolites (gas chromatography-mass spectrometry platform), and their correlation (Pearson correlation analysis) was investigated after 14 days repeated oral exposure in mice. β-CD did not significantly affect the α-diversity indexes, including Richness, Chao1, Shannon and Simpson indexes, but disturbed the structure of the gut bacteria according to the result of principal component analysis (PCA). After taxonomic assignment, 1 in 27 phyla, 2 in 48 classes, 3 in 107 orders, 6 in 192 families, and 8 in 332 genera were significantly different between control and β-CD treated groups. The serum metabolites were significantly changed after β-CD treatment according to the result of unsupervized PCA and supervised partial least squares-discriminant analysis (PLS-DA). A total of 112 differential metabolites (89 downregulated and 23 upregulated) were identified based on the VIP >1 from orthogonal PLS-DA and <0.05 from Student's -test. The metabolic pathways, including ABC transporters, pyrimidine metabolism, purine metabolism, glucagon signaling pathway, insulin signaling pathway, and glycolysis/gluconeogenesis, were enriched by KEGG pathway analysis. Our study provides a general observation of gut microbiota, serum metabolites and their correlation after exposure to β-CD in mice, which will be helpful for future research and application of β-CD.

摘要

具有疏水空腔的β-环糊精(β-CD)能够与有机分子形成包合物。主客体复合物的形成使得β-CD在许多领域得到广泛应用,但其与生物体的相互作用尚不清楚。在本研究中,对小鼠进行14天重复口服暴露后,研究了β-CD对肠道微生物群(16S rRNA基因测序)、血清代谢物(气相色谱-质谱平台)及其相关性(Pearson相关性分析)的影响。β-CD对包括丰富度、Chao1、香农和辛普森指数在内的α-多样性指数没有显著影响,但根据主成分分析(PCA)结果,其扰乱了肠道细菌的结构。经过分类学归属后,对照和β-CD处理组之间在27个门中有1个、48个纲中有2个、107个目中有3个、192个科中有6个、332个属中有8个存在显著差异。根据无监督PCA和有监督的偏最小二乘判别分析(PLS-DA)结果,β-CD处理后血清代谢物发生了显著变化。基于正交PLS-DA中VIP>1和学生t检验中P<0.05,共鉴定出112种差异代谢物(89种下调和23种上调)。通过KEGG通路分析,富集了包括ABC转运蛋白、嘧啶代谢、嘌呤代谢、胰高血糖素信号通路、胰岛素信号通路和糖酵解/糖异生等代谢通路。我们的研究对小鼠暴露于β-CD后的肠道微生物群、血清代谢物及其相关性进行了总体观察,这将有助于β-CD未来的研究和应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfc/7845417/be9654fd4265/fphar-11-574607-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfc/7845417/56fbe23d965c/fphar-11-574607-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfc/7845417/be9654fd4265/fphar-11-574607-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfc/7845417/56fbe23d965c/fphar-11-574607-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfc/7845417/be9654fd4265/fphar-11-574607-g003.jpg

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