Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target-Reference-Cited by-同舟云学术

Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target

Published:2023-08-04 Issue:6657 Volume:381 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Wang Kai¹²^ORCID,Zhang Zhiwei¹²^ORCID,Hang Jing¹³⁴^ORCID,Liu Jia⁵^ORCID,Guo Fusheng⁶⁷^ORCID,Ding Yong¹²^ORCID,Li Meng¹²^ORCID,Nie Qixing¹²^ORCID,Lin Jun¹²,Zhuo Yingying¹²,Sun Lulu⁸,Luo Xi¹²,Zhong Qihang¹³⁴,Ye Chuan¹²,Yun Chuyu¹²,Zhang Yi¹²^ORCID,Wang Jue⁶^ORCID,Bao Rui⁹^ORCID,Pang Yanli¹³⁴^ORCID,Wang Guang⁵^ORCID,Gonzalez Frank J.⁸^ORCID,Lei Xiaoguang⁶⁷^ORCID,Qiao Jie¹³⁴¹⁰^ORCID,Jiang Changtao¹²¹¹^ORCID

Affiliation:

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.

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.

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.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.add5787

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