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The Potential Role of the Dipeptidyl Peptidase-4-Like Activity From the Gut Microbiota on the Host Health.

ABSTRACT: The Dipeptidyl peptidase-4 (DPP-4) activity influences metabolic, behavioral and intestinal disorders through the cleavage of key hormones and peptides. Some studies describe the existence of human DPP-4 homologs in commensal bacteria, for instance in Prevotella or Lactobacillus. However, the role of the gut microbiota as a source of DPP-4-like activity has never been investigated. Through the comparison of the DPP-4 activity in the cecal content of germ-free mice (GFM) and gnotobiotic mice colonized with the gut microbiota of a healthy subject, we bring the proof of concept that a significant DPP-4-like activity occurs in the microbiota. By analyzing the existing literature, we propose that DPP-4-like activity encoded by the intestinal microbiome could constitute a novel mechanism to modulate protein digestion as well as host metabolism and behavior.

SUBMITTER: Olivares M

PROVIDER: S-EPMC6113382 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Potential Role of the Dipeptidyl Peptidase-4-Like Activity From the Gut Microbiota on the Host Health.

Olivares Marta M Schüppel Valentina V Hassan Ahmed M AM Beaumont Martin M Neyrinck Audrey M AM Bindels Laure B LB Benítez-Páez Alfonso A Sanz Yolanda Y Haller Dirk D Holzer Peter P Delzenne Nathalie M NM

Frontiers in microbiology 20180822

The Dipeptidyl peptidase-4 (DPP-4) activity influences metabolic, behavioral and intestinal disorders through the cleavage of key hormones and peptides. Some studies describe the existence of human DPP-4 homologs in commensal bacteria, for instance in <i>Prevotella</i> or <i>Lactobacillus</i>. However, the role of the gut microbiota as a source of DPP-4-like activity has never been investigated. Through the comparison of the DPP-4 activity in the cecal content of germ-free mice (GFM) and gnotobi ...[more]

PMID: 30186247

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Project description:Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine. Linagliptin is also the most potent DPP-4 inhibitor, has the highest affinity for this protein, and has the largest volume of distribution; these properties allow linagliptin to penetrate kidney tissue and tightly bind resident DPP-4. In animal models of kidney disease, linagliptin elicited multiple renoprotective effects, including reducing albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis, independent of changes in glucagon-like peptide-1 (GLP-1) and glucose levels. At the molecular level, linagliptin prevented the pro-fibrotic endothelial-to-mesenchymal transition by disrupting the interaction between membrane-bound DPP-4 and integrin ?1 that enhances signaling by transforming growth factor-?1 and vascular endothelial growth factor receptor-1. Linagliptin also increased stromal cell derived factor-1 levels, ameliorated endothelial dysfunction, and displayed unique antioxidant effects. Although the nephroprotective effects of linagliptin are yet to be translated to the clinical setting, the ongoing Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®) study will definitively assess the renal effects of this DPP-4 inhibitor. CARMELINA® is the only clinical trial of a DPP-4 inhibitor powered to evaluate kidney outcomes.

Dataset Information

The Potential Role of the Dipeptidyl Peptidase-4-Like Activity From the Gut Microbiota on the Host Health.

Publications

The Potential Role of the Dipeptidyl Peptidase-4-Like Activity From the Gut Microbiota on the Host Health.

Similar Datasets

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