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
{"title":"微生物宿主同工酶分析显示微生物DPP4是一个潜在的抗糖尿病靶点。","authors":"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","doi":"10.1126/science.add5787","DOIUrl":null,"url":null,"abstract":"<div >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.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"381 6657","pages":""},"PeriodicalIF":44.7000,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"11","resultStr":"{\"title\":\"Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target\",\"authors\":\"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\",\"doi\":\"10.1126/science.add5787\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >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.</div>\",\"PeriodicalId\":21678,\"journal\":{\"name\":\"Science\",\"volume\":\"381 6657\",\"pages\":\"\"},\"PeriodicalIF\":44.7000,\"publicationDate\":\"2023-08-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"11\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/science.add5787\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/science.add5787","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target
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.
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