研究人员开发了一个酶活性筛选平台，用于研究肠道微生物群衍生酶如何影响宿主的生理机能。研究人员发现，微生物群中的特定细菌类群表达二肽基肽酶4（DPP4）。微生物DPP4能够降低胰高血糖素样肽-1（GLP-1）的活性，并破坏肠漏小鼠的葡萄糖代谢。此外，目前针对人类DPP4的药物（包括西他列汀）对微生物DPP4几乎没有影响。通过高通量筛选，研究人员发现了一种可改善糖尿病小鼠葡萄糖耐量的选择性微生物DPP4抑制剂——蝙蝠葛苏林碱-d4（Dau-d4）。
据悉，从机理上了解微生物蛋白如何影响宿主，可以更深入地了解肠道微生物群与宿主的交流。
附：英文原文
Title: Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target
Author: Kai Wang, Zhiwei Zhang, Jing Hang, Jia Liu, Fusheng Guo, Yong Ding, Meng Li, Qixing Nie, Jun Lin, Yingying Zhuo, Lulu Sun, Xi Luo, Qihang Zhong, Chuan Ye, Chuyu Yun, Yi Zhang, Jue Wang, Rui Bao, Yanli Pang, Guang Wang, Frank J. Gonzalez, Xiaoguang Lei, Jie Qiao, Changtao Jiang
Issue&Volume: 2023-08-04
Abstract: A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota–host cross-talk. We developed an enzyme activity–screening platform to investigate how gut microbiota–derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.
DOI: add5787
Source: https://www.science.org/doi/full/10.1126/science.add5787