Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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.
See this image and copyright information in PMC

Comment in

References

    1. Ahmed R. H., Huri H. Z., Muniandy S., Al-Hamodi Z., Al-Absi B., Alsalahi A., et al. . (2017). Altered circulating concentrations of active glucagon-like peptide (GLP-1) and dipeptidyl peptidase 4 (DPP4) in obese subjects and their association with insulin resistance. Clin. Biochem. 50, 746–749. 10.1016/j.clinbiochem.2017.03.008 - DOI - PubMed
    1. Anastasiou R., Papadelli M., Georgalaki M. D., Kalantzopoulos G., Tsakalidou E. (2002). Cloning and sequencing of the gene encoding X-prolyl-dipeptidyl aminopeptidase (PepX) from Streptococcus thermophilus strain ACA-DC 4. J. Appl. Microbiol. 93, 52–59. 10.1046/j.1365-2672.2002.01659.x - DOI - PubMed
    1. Anderberg R. H., Richard J. E., Hansson C., Nissbrandt H., Bergquist F., Skibicka K. P. (2016). GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality. Psychoneuroendocrinology 65, 54–66. 10.1016/j.psyneuen.2015.11.021 - DOI - PubMed
    1. Bansal T., Alaniz R. C., Wood T. K., Jayaraman A. (2010). The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc. Natl. Acad. Sci. U.S.A. 107, 228–233. 10.1073/pnas.0906112107 - DOI - PMC - PubMed
    1. Blachier F., Mariotti F., Huneau J. F., Tomé D. (2007). Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids 33, 547–562. 10.1007/s00726-006-0477-9 - DOI - PubMed

LinkOut - more resources