The rapid proliferation and colonization of probiotics in the intestines are essential for human health. Quorum sensing (QS) is a communication mechanism among bacteria, which can regulate various bacterial crowd behavior. This study aimed to enhance the viability of Lactobacillus reuteri 1-12 by regulating QS. Herein, we built a database containing 72 natural products (previously reported) that can improve intestinal flora. Virtual screening (VS) was subsequently conducted to screen four potential active compounds. After that, molecular docking was conducted to analyze the binding mode of the four natural products to S-Ribosylhomocysteinase (LuxS). The results showed that norathyriol, mangiferin, baicalein, and kaempferol had good binding ability to LuxS. The validation experiment showed that norathyriol, mangiferin, baicalein, and kaempferol could inhibit the production of autoinducer-2 (AI-2). Moreover, mangiferin significantly increased L. reuteri 1-12 biomass and promoted L. reuteri 1-12 biofilm formation and structure. Besides, only mangiferin inhibited luxS expression, thus increasing L. reuteri 1-12 biomass. This research indicated that mangiferin may be a potential inhibitor of LuxS, promoting the probiotic properties of L. reuteri and human health.
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