Lactobacilli possess inhibitory activity against dipeptidyl peptidase-4 (DPP-4)

Abstract

Dipeptidyl peptidase-4 (DPP-4) plays an important role in the enzymatic inactivation of incretin hormones. In this context, drugs that inhibit DPP-4 have been developed and clinically approved as therapies for type 2 diabetes. As the primary substrates of DPP-4 are produced in the intestinal lining, we investigated whether lactobacilli colonizing the gut could inhibit this enzyme. Fifteen Lactobacillus strains (Lb 1-15) from human infant faecal samples were isolated, identified, extracted and screened for inhibitory activity against DPP-4. Activity was compared against Lactobacillus reference strains (Ref 1-7), a Gram-positive control (Ctrl 1) and two Gram-negative controls (Ctrl 2-3). A range of DPP-4 inhibitory activity was observed (10-32 %; p<0.05-0.001). Strains of L. plantarum (12-25 %) and L. fermentum (14 %) had significant inhibitory activity. However, we noted that Escherichia coli (Ctrl 2) and Salmonella Typhimurium (Ctrl 3) had the greatest inhibitory activity (30-32 %). Contrastingly, some isolates (Lb 12-15) and reference cultures (Ref 1-4), instead of inhibiting DPP-4, actually enhanced it, perhaps indicating the presence of X-prolyldipeptidyl-amino-peptidase (PepX). This provides a future rationale for using probiotic bacteria or their components for management of type 2 diabetes via DPP-4 inhibition.

Screening for Potential Novel Probiotics With Dipeptidyl Peptidase IV-Inhibiting Activity for Type 2 Diabetes Attenuation in vitro and in vivo

“…NC, normal control group; DC, diabetic control group; LG, DC plus L. rhamnosus GG; LA, DC plus L. acidophilus KLDS1.0901. activity with L. acidophilus KLDS1.1003 and L. acidophilus KLDS1.0901, which was consistent with other studies (Panwar et al, 2015;Zhu et al, 2016). However, it was observed that DPP-IV inhibitory levels were higher in previous studies; this may be due to different concentrations of bacteria or sources of DPP-IV.…”

Some current applications, limitations and future perspectives of lactic acid bacteria as probiotics

“…Based on these, Yun et al [ 49 ] speculated that LAB in breast milk could be one of the important ingredients present for the prevention of diabetes and thus recommended further studies on this. In another study by Panwar et al [ 54 ], some LAB strains ( L. rhamnosus, L. plantarum, L. johnsonii, L. acidophilus and L. casei ) were able to stimulate the secretion of gut hormones GLP-1 and GIP which play a key role in modulating insulin secretion and inhibition of DPP IV. This study showed that probiotic LABs may be used as modulators of incretin hormones which can be explored as potential bio-therapeutics against diabetes.…”

“… [ 57 ] Lactobacillus spp Significant DPP-IV inhibitory activity, this varied among the strains studied. [ 54 ] Lactobacillus sakei OK67 Inhibition of HFD-induced body and epididymal fat weight gain, HFD-induced TNF-α and IL-ß expression. Inhibition of NF-kB activation in the colon.…”

Bacillus As Potential Probiotics: Status, Concerns, and Future Perspectives

“…diarrhea, inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, cancer etc. ( Mallappa et al, 2012 ; Panwar et al, 2014 , 2016 ; Ranji et al, 2015 ). It has been clearly understood that the gut inhabitants and their proper balance is the foremost criteria that determines healthy status, particularly in terms of metabolic disorders ( Wang et al, 2015 ).…”