Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target
Creators: name: Nie, Qixing
name: Luo, Xi
name: Gonzalez, Frank J.
name: Wang, Kai
name: Zhang, Zhiwei
name: Hang, Jing
name: Liu, Jia
name: Guo, Fusheng
name: Ding, Yong
name: Li, Meng
name: Nie, Qi-Xing
name: Lin, Jun
name: Zhuo, Yingying
name: Sun, Lulu
name: Zhong, Qihang
name: Ye, Chuan
name: Yun, Chuyu
name: Zhang, Yi
name: Wang, Jue
name: Bao, Rui
name: Pang, Yanli
name: Wang, Guang
name: Gonzalez, Frank
name: Lei, Xiaoguang
name: Qiao, Jie
name: Jiang, Changtao
Publisher: name: Zenodo
Year: 2023
Subjects: Multidisciplinary

description: 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.
description: Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 82288102Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 82130022Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 31925021Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 91857115Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 92149306Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 82071658Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 81921001Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 22193073Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 92253305Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 2018YFA0800700Funding provided by: National Natural Science Foundation of China<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809<br>Award Number: 2022YFC3401500Funding provided by: Beijing Nova Program<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100005090<br>Award Number: Z201100006820010Funding provided by: National Postdoctoral Program for Innovative Talents<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100012152<br>Award Number: BX20190019Funding provided by: National Cancer Institute<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054<br>Award Number: ZIABC005708Funding provided by: the Beijing Outstanding Young Scientist Program<br>Award Number: BJJWZYJH01201910001001