Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target
Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target
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DOI：
10.1126/science.add5787
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发表时间：
2023-08-04
期刊：
影响因子：
56.9
通讯作者：
Jiang, Changtao
中科院分区：
文献类型：
--
作者：
Wang, Kai;Zhang, Zhiwei;Jiang, Changtao
从机制上理解微生物蛋白质如何影响宿主可以更深入地了解肠道微生物区系与宿主之间的相互作用。我们开发了一个酶活性筛选平台来研究肠道微生物区系衍生的酶如何影响宿主生理。我们发现二肽基肽酶4(DPP4)是由微生物区系中特定的细菌类群表达的。微生物DPP4能降低GLP-1活性，扰乱肠漏小鼠的糖代谢。此外，目前针对人DPP4的药物，包括西格列汀，对微生物DPP4几乎没有影响。通过高通量筛选，我们确定蝙蝠葛苏林-d4(DAU-d4)是一种选择性的微生物DPP4抑制剂，可以改善糖尿病小鼠的糖耐量。
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.