Screening of quorum-sensing inhibitors of intestinal probiotic Lactobacillus reuteri in natural products

Recently, Biomedicine & Pharmacotherapy (IF=6.
529) published online the research paper titled "Virtual screening and in vitro experimental verification of LuxS inhibitors from natural products for Lactobacillus reuteri" by the Yunnan Provincial Key Laboratory of Sustainable Utilization of Southern Medicine, which was reported for the first time.
Mangiferin, an active ingredient widely distributed in natural medicines such as mango, Anemarrhena, Dian gentian, swedia, and myrobalan, is a quorum-sensing protein LuxS inhibitor in the probiotic Lactobacillus reuteri, and in vitro experiments show that mangiferin can It can effectively promote the growth, proliferation and biofilm formation of the probiotic L.
reuteri, which may be a prebiotic with great potential
.

The presence of probiotics in the gut is essential for human health, and L.
reuteri is present in the guts of nearly all vertebrates
.

L.
reuteri has strong adhesion to the intestinal mucosa, which can antagonize the colonization of harmful bacteria and improve the immune function of the host
.

Studies have shown that L.
reuteri has numerous benefits for host health
.

The National Health Commission approved L.
reuteri to be used in health food and infant food in 2003 and 2014, respectively
.

At present, L.
reuteri has become a probiotic species with great research value
.

The communication method between bacteria is called quorum sensing.
According to research reports, AI-2 (Autoinducer-2) is a common "communication language" among bacterial species, which is closely related to bacterial growth, biofilm formation, virulence factor expression, and clustering.
Exercise and bacterial metabolism are closely related
.

LuxS can catalyze the formation of AI-2 from SRH.
The concentration of extracellular AI-2 increases with the increase of bacterial density.
When AI-2 reaches a certain concentration threshold, bacteria will internalize it into the body to regulate the biological behavior of bacteria
.

Competitively inhibiting the production of AI-2 and delaying the time when the concentration of AI-2 reaches the threshold may allow probiotics to continue to grow and proliferate
.

Therefore, screening LuxS inhibitors to induce rapid proliferation and colonization of L.
reuteri from the perspective of quorum sensing will be an effective strategy to stimulate the probiotic properties of probiotics
.

Figure 1.
Graphical summary.
Based on homology modeling, the study constructed the 3D structure of LuxS and screened four potential LuxS inhibitors (mangiferin, mangiferin, baicalein) among 72 natural products by virtual screening.
, kaempferol), molecular dynamics simulation results show that mangiferin aglycone, mangiferin and LuxS have stable binding conformations
.

In addition, the four natural products screened can inhibit the production of AI-2 to varying degrees, and only mangiferin showed the ability to promote the growth and proliferation of L.
reuteri, and also showed outstanding contributions in biofilm formation and structure improvement , which may be related to the inhibition of luxS gene expression by mangiferin
.

Studies have shown that mangiferin may be a LuxS inhibitor that contributes to the probiotic properties of L.
reuteri and to human health
.

Figure 2.
Effects of candidate compounds on L.
reuteri (AD) Effects of candidate compounds on L.
reuteri growth; (EH) Effects of candidate compounds on L.
reuteri AI-2 content; (IL) Candidate compounds on L.
reuteri organisms The effect of film formation
.

*P < 0.
05, **P < 0.
01, ***P < 0.
001, ****P < 0.
0001 compared to blank group
.

Figure 3.
Effects of candidate compounds on Lactobacillus reuteri biofilm morphology.
From left to right, scanning electron microscopy at 5000X, 10000X, and 15000X magnification in the same field of view
.

(A) blank group; (B) mangiferin aglycone (60 μM); (C) mangiferin (60 μM); (D) baicalein (60 μM); (E) kaempferol (60 μM)
.

The research work is part of the Yunnan Provincial Key Laboratory of Sustainable Utilization of Southern Medicine and Yunnan Province's work on the exploration, development and utilization of traditional medicine resources in the Lancang-Mekong region for metabolic diseases in South Asia and Southeast Asia
.

Relevant work was supported by the National Natural Science Foundation of China (81660684, 81760733, 81960710); the Yunnan Provincial Applied Basic Research Project (2019IB009, 2018FF001-(005), 202001AZ070 001-037, 202002AA100007); the Yunnan Provincial Department of Education Research Fund Project (2020Y0224) Fund support
.

Paper link: https://