Autoinducer-2 promotes the colonization of <i>Lactobacillus rhamnosus GG</i> to improve the intestinal barrier function in a neonatal mouse model of antibiotic-induced intestinal dysbiosis

作者全名："Hu, Riqiang; Yang, Ting; Ai, Qing; Shi, Yuan; Ji, Yanchun; Sun, Qian; Tong, Bei; Chen, Jie; Wang, Zhengli"

作者地址："[Hu, Riqiang; Yang, Ting; Tong, Bei; Chen, Jie; Wang, Zhengli] Chongqing Med Univ, Childrens Hosp,Childrens Nutr Res Ctr, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Chongqin, Chongqing, Peoples R China; [Ai, Qing; Shi, Yuan; Ji, Yanchun; Sun, Qian; Wang, Zhengli] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Neonatol, Childrens Hosp, Chongqing, Peoples R China; [Wang, Zhengli] Chongqing Med Univ, Jiangxi Hosp, Affiliated Childrens Hosp, Chongqing, Peoples R China"

通信作者："Chen, J; Wang, ZL (通讯作者)，Chongqing Med Univ, Childrens Hosp,Childrens Nutr Res Ctr, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Chongqin, Chongqing, Peoples R China.; Wang, ZL (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Neonatol, Childrens Hosp, Chongqing, Peoples R China.; Wang, ZL (通讯作者)，Chongqing Med Univ, Jiangxi Hosp, Affiliated Childrens Hosp, Chongqing, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001164049400006

JCR分区：Q1

影响因子：7.4

年份：2024

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Autoinducer-2; Lactobacillus rhamnosus GG; Intestinal barrier function; Antibiotics-induced intestinal flora; Tight junctions; Butyric acid; Hydroxycarboxylic acid receptor 2; Biofilm

摘要："Background Human health is seriously threatened by antibiotic-induced intestinal disorders. Herein, we aimed to determine the effects of Autoinducer-2 (AI-2) combined with Lactobacillus rhamnosus GG (LGG) on the intestinal barrier function of antibiotic-induced intestinal dysbiosis neonatal mice. Methods An antibiotic-induced intestinal dysbiosis neonatal mouse model was created using antibiotic cocktails, and the model mice were randomized into the control, AI-2, LGG, and LGG + AI-2 groups. Intestinal short-chain fatty acids and AI-2 concentrations were detected by mass spectrometry and chemiluminescence, respectively. The community composition of the gut microbiota was analyzed using 16S rDNA sequencing, and biofilm thickness and bacterial adhesion in the colon were assessed using scanning electron microscopy. Transcriptome RNA sequencing of intestinal tissues was performed, and the mRNA and protein levels of HCAR2 (hydroxycarboxylic acid receptor 2), claudin3, and claudin4 in intestinal tissues were determined using quantitative real-time reverse transcription PCR and western blotting. The levels of inflammatory factors in intestinal tissues were evaluated using enzyme-linked immunosorbent assays (ELISAs). D-ribose, an inhibitor of AI-2, was used to treat Caco-2 cells in vitro. Results Compared with the control, AI-2, and LGG groups, the LGG + AI-2 group showed increased levels of intestinal AI-2 and proportions of Firmicutes and Lacticaseibacillus, but a reduced fraction of Proteobacteria. Specifically, the LGG + AI-2 group had considerably more biofilms and LGG on the colon surface than those of other three groups. Meanwhile, the combination of AI-2 and LGG markedly increased the concentration of butyric acid and promoted Hcar2, claudin3 and claudin4 expression levels compared with supplementation with LGG or AI-2 alone. The ELISAs revealed a significantly higher tumor necrosis factor alpha (TNF-alpha) level in the control group than in the LGG and LGG + AI-2 groups, whereas the interleukin 10 (IL-10) level was significantly higher in the LGG + AI-2 group than in the other three groups. In vitro, D-ribose treatment dramatically suppressed the increased levels of Hcar2, claudin3, and claudin4 in Caco-2 cells induced by AI-2 + LGG. Conclusions AI-2 promotes the colonization of LGG and biofilm formation to improve intestinal barrier function in an antibiotic-induced intestinal dysbiosis neonatal mouse model."

基金机构：National Science Foundation of China

基金资助正文："We are grateful to all study participants for their contributions. We also thank the native English speaking scientists of Elixigen Company (Huntington Beach, California) for editing our manuscript."