Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target
Year: 2023
Type: article
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.
Source: Science
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
Institutions: Peking University, Peking University Third Hospital, Capital Medical University, Beijing Chao-Yang Hospital, Capital Medical University, Beijing National Laboratory for Molecular Sciences, Center for Life Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering, Ministry of Education, National Institutes of Health, National Cancer Institute, Center for Cancer Research, Sichuan University, West China Hospital of Sichuan University, State Key Laboratory of Biotherapy
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4385563404