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Dryad
Published August 31, 2023 | Version v1
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Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target

Creators

  • 1. Peking University
  • 2. National Cancer Institute
  • 3. Peking University Third Hospital
  • 4. Capital Medical University
  • 5. West China Hospital of Sichuan University

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.

Notes

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 82288102

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 82130022

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 31925021

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 91857115

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 92149306

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 82071658

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 81921001

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 22193073

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 92253305

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 2018YFA0800700

Funding provided by: National Natural Science Foundation of China
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001809
Award Number: 2022YFC3401500

Funding provided by: Beijing Nova Program
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100005090
Award Number: Z201100006820010

Funding provided by: National Postdoctoral Program for Innovative Talents
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100012152
Award Number: BX20190019

Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: ZIABC005708

Funding provided by: the Beijing Outstanding Young Scientist Program
Award Number: BJJWZYJH01201910001001

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Additional details

Related works

Is cited by
10.1126/science.add5787 (DOI)
Is derived from
10.5061/dryad.b2rbnzsmq (DOI)