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基于微生物组的治疗方法的转化开发：大肠杆菌 Nissle 和工程菌株在人类和非人类灵长类动物中的动力学。

Translational Development of Microbiome-Based Therapeutics: Kinetics of E. coli Nissle and Engineered Strains in Humans and Nonhuman Primates.

机构信息

Synlogic, Cambridge, Massachusetts, USA.

Human Predictions, Cambridge, Massachusetts, USA.

出版信息

Clin Transl Sci. 2018 Mar;11(2):200-207. doi: 10.1111/cts.12528. Epub 2017 Dec 1.

DOI:10.1111/cts.12528
PMID:29194983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5866967/
Abstract

Understanding the pharmacology of microbiome-based therapeutics is required to support the development of new medicines. Strains of E. coli Nissle (EcN) were genetically modified and administered to cynomolgus monkeys at doses of 1 × 10 and 1 × 10 colony-forming units (CFU)/day for 28 days. A clinical study to evaluate the exposure and clearance of EcN in healthy volunteers was also performed. Healthy subjects received oral doses of EcN, 2.5 to 25 × 10 CFU 3 times daily for 28 days or a single day. In cynomolgus monkeys, replicating strains yielded higher fecal concentrations than nonreplicating strains and persisted for longer following cessation of dosing. In the clinical study, all subjects cleared EcN following cessation of dosing with median clearance of 1 week. Quantitative methodology can be applied to microbiome-based therapeutics, and similar kinetics and clearance were observed for EcN in cynomolgus monkeys and humans.

摘要

需要了解基于微生物组的治疗药物的药理学，以支持新药的开发。经过基因改造的大肠杆菌菌株 Nissle (EcN) 以 1×10 和 1×10 菌落形成单位 (CFU)/天的剂量施用于食蟹猴，持续 28 天。还进行了一项临床研究，以评估 EcN 在健康志愿者中的暴露和清除情况。健康受试者口服 EcN，每天 3 次，每次 2.5 到 25×10 CFU，持续 28 天或 1 天。在食蟹猴中，复制株比非复制株产生更高的粪便浓度，并且在停止给药后持续更长时间。在临床研究中，所有受试者在停止给药后清除 EcN，中位清除时间为 1 周。定量方法可应用于基于微生物组的治疗药物，并且在食蟹猴和人类中观察到 EcN 的类似动力学和清除率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/8199261df08e/CTS-11-200-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/3926034f3d4e/CTS-11-200-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/37aaa32c8977/CTS-11-200-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/479ffac510c8/CTS-11-200-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/8199261df08e/CTS-11-200-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/3926034f3d4e/CTS-11-200-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/37aaa32c8977/CTS-11-200-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/479ffac510c8/CTS-11-200-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f266/5866967/8199261df08e/CTS-11-200-g004.jpg

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