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脂化亚麻酸对的活性及其对人肠道细菌的影响。

The Activity of Liposomal Linolenic Acid Against and Its Impact on Human Fecal Bacteria.

机构信息

Key Laboratory of Digestive Diseases of Jiangxi, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

School of Pharmacy, Nanchang University, Nanchang, China.

出版信息

Front Cell Infect Microbiol. 2022 May 17;12:865320. doi: 10.3389/fcimb.2022.865320. eCollection 2022.

Abstract

() infection is associated with a variety of gastrointestinal diseases. Here, we focused on the activity of a novel nanomedicine-liposomal linolenic acid (LipoLLA) against and its impact on human fecal bacteria . The minimum inhibitory concentrations (MICs) of LipoLLA against 30 clinical strains were determined in combination with amoxicillin (AMX), metronidazole (MTZ), levofloxacin (LVFX) and clarithromycin (CAM). Bactericidal activity was measured by generating concentration-bactericidal curves at different times and pH values. Leakage of glucose (GLU) and aspartate aminotransferase (AST) was detected, combined with detection of changes in morphology by electron microscopy, to study the mechanism of action of LipoLLA against . The effect of LipoLLA on human fecal bacteria was studied by high-throughput sequencing of fecal samples. We observed a synergistic or additive effect when LipoLLA was combined with AMX, MTZ, LVFX and CAM. The concentration-sterilization curves were pH and time dependent. After treatment with LipoLLA, GLU and AST levels were increased (P<0.05), and the morphology of changed significantly. Moreover, LipoLLA activity led to no significant changes in the intestinal flora in terms of alpha diversity, species composition, beta diversity, etc. In conclusion, LipoLLA showed good anti- effects. It destroyed the outer membrane barrier and caused leakage of the bacterial contents to achieve anti- effects. And LipoLLA had little effect on human fecal bacteria .

摘要

()感染与多种胃肠道疾病有关。在这里,我们专注于一种新型纳米药物-脂亚麻酸(LipoLLA)对 的活性及其对人粪便细菌的影响。采用联合阿莫西林(AMX)、甲硝唑(MTZ)、左氧氟沙星(LVFX)和克拉霉素(CAM)的方法测定 LipoLLA 对 30 株临床分离株的最低抑菌浓度(MIC)。通过在不同时间和 pH 值下生成浓度杀菌曲线来测量杀菌活性。检测葡萄糖(GLU)和天冬氨酸氨基转移酶(AST)的泄漏情况,并结合电镜观察形态变化,研究 LipoLLA 对 的作用机制。通过对粪便样本进行高通量测序研究 LipoLLA 对人粪便细菌的影响。当 LipoLLA 与 AMX、MTZ、LVFX 和 CAM 联合使用时,观察到协同或相加作用。浓度杀菌曲线依赖于 pH 值和时间。用 LipoLLA 处理后,GLU 和 AST 水平升高(P<0.05), 的形态明显改变。此外,LipoLLA 活性对肠道菌群的 alpha 多样性、物种组成、beta 多样性等方面没有显著影响。总之,LipoLLA 表现出良好的抗菌作用。它破坏了外膜屏障,导致细菌内容物泄漏,从而达到抗菌作用。而且 LipoLLA 对人粪便细菌的影响很小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/592f/9152453/0a46a97039da/fcimb-12-865320-g001.jpg

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