Back to Search
Start Over
Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target.
- Source :
-
Science (New York, N.Y.) [Science] 2023 Aug 04; Vol. 381 (6657), pp. eadd5787. Date of Electronic Publication: 2023 Aug 04. - Publication Year :
- 2023
-
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.
- Subjects :
- Animals
Humans
Mice
Feces microbiology
Glucagon-Like Peptide 1 metabolism
Glucose metabolism
Isoenzymes metabolism
Sitagliptin Phosphate pharmacology
Sitagliptin Phosphate therapeutic use
Bacteroides drug effects
Bacteroides enzymology
Bacteroides genetics
Diabetes Mellitus, Type 2 enzymology
Diabetes Mellitus, Type 2 microbiology
Dipeptidyl Peptidase 4 metabolism
Dipeptidyl-Peptidase IV Inhibitors pharmacology
Dipeptidyl-Peptidase IV Inhibitors therapeutic use
Gastrointestinal Microbiome
Host Microbial Interactions
Hypoglycemic Agents pharmacology
Hypoglycemic Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 381
- Issue :
- 6657
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 37535747
- Full Text :
- https://doi.org/10.1126/science.add5787