机构：[1]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Peking University, Beijing, China.[2]Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.[3]Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.[4]National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China.[5]Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.北京朝阳医院[6]Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Peking University, Beijing, China.[7]Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.[8]Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.[9]Center of Infectious Diseases, Division of Infectious Diseases in State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.四川大学华西医院[10]Beijing Advanced Innovation Center for Genomics, Beijing, China.[11]Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, China.
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.
基金：
This work was supported by the National
Natural Science Foundation of the Peoples’ Republic of China (grant
nos. 82288102, 82130022, and 31925021), the National Key Research
and Development Program of China (grant nos. 2018YFA0800700,
2022YFA0806400, and 2022YFC3401500), the National Natural
Science Foundation of the Peoples’ Republic of China (grant nos.
91857115, 92149306, 82071658, 81921001, 22193073, 92253305, and
32000813), the National Cancer Institute Intramural Research Program
(grant no. ZIABC005708), the Beijing Nova Program (grant no.
Z201100006820010), the Beijing Outstanding Young Scientist Program
(grant no. BJJWZYJH01201910001001), and the National Postdoctoral
Program for Innovative Talents (grant no. BX20190019).
第一作者机构：[1]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Peking University, Beijing, China.[2]Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Peking University, Beijing, China.[2]Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.[3]Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.[4]National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China.[6]Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Peking University, Beijing, China.[7]Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.[10]Beijing Advanced Innovation Center for Genomics, Beijing, China.[11]Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, China.
推荐引用方式(GB/T 7714)：
Wang Kai,Zhang Zhiwei,Hang Jing,et al.Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target[J].SCIENCE.2023,381(6657):501-+.doi:10.1126/science.add5787.
APA：
Wang Kai,Zhang Zhiwei,Hang Jing,Liu Jia,Guo Fusheng...&Jiang Changtao.(2023).Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target.SCIENCE,381,(6657)
MLA：
Wang Kai,et al."Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target".SCIENCE 381..6657(2023):501-+
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