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. 2018 Aug 22:9:1900.
doi: 10.3389/fmicb.2018.01900. eCollection 2018.

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

Marta Olivares  1 , Valentina Schüppel  2   3 , Ahmed M Hassan  4 , Martin Beaumont  1 , Audrey M Neyrinck  1 , Laure B Bindels  1 , Alfonso Benítez-Páez  5 , Yolanda Sanz  5 , Dirk Haller  2   3 , Peter Holzer  4 , Nathalie M Delzenne  1
Affiliations

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

Marta Olivares et al. Front Microbiol. .

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.

Keywords: DPP-4 activity; PepX activity; behavior; gut microbiota; metabolism; microbiome.

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Figures

Figure 1
Figure 1
Families with X-prolyl dipeptidyl aminopeptidase activities. The S9B family includes the Dipeptidyl peptidase-4 activity form mammalian cells and Gram-negative bacteria (Prevotella). The counterpart activity, so-called Xaa-Pro dipeptidyl peptidase or PepX activity is present in Gram-positive bacteria (Lactobacillus, Lactococcus, Streptococcus).
Figure 2
Figure 2
Dipeptidyl peptidase-4 in the (A) cecal content and (B) cecal tissue, and (C) Dpp4 expression in the cecal tissue of germ-free mice (GFM) and mice colonized with healthy gut microbiota. Data were analyzed with the t-test for unpaired samples. Significant differences are represented by the symbol ***(p < 0.001).
Figure 3
Figure 3
Theoretical scenarios in which the Dipeptidyl peptidase-4 and PepX activities produced by the gut microbiota might impact host's health through the proteolysis of different substrates with a biological activity. Glucagon-like peptide-1 (GLP)-1, gastric inhibitory polypeptide (GIP), and peptide YY (PYY) are represented in color (purple, green and blue, respectively) when not cleaved by DPP-4 and PepX activities. The corresponding symbols are represented in black after the cleavage by DPP-4 and PepX activities.
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