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

• Published in: Journal of translational medicine Vol. 22; no. 1; pp. 177 - 18
• Main Authors: Hu, Riqiang, Yang, Ting, Ai, Qing, Shi, Yuan, Ji, Yanchun, Sun, Qian, Tong, Bei, Chen, Jie, Wang, Zhengli
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.02.2024; BioMed Central; BMC
• Subjects: Analysis; Animal models; Animals; Animals, Newborn; Anti-Bacterial Agents - pharmacology; Antibiotics; Antibiotics-induced intestinal flora; Autoinducer-2; Biofilms; Butyric acid; Caco-2 Cells; Cell signaling; Chemiluminescence; Claudin-4 - metabolism; Colon; Colonization; Colorectal diseases; Community composition; Complications and side effects; Composition; D-Ribose; Dosage and administration; Drug therapy; Dysbacteriosis; Dysbiosis; Feces; Gastrointestinal diseases; Gene expression; Genetic aspects; Health aspects; Humans; Inflammation; Interleukin 10; Intestinal Barrier Function; Intestinal microflora; Intestine; Lacticaseibacillus rhamnosus; Lactobacillus rhamnosus; Lactobacillus rhamnosus GG; Mass spectroscopy; Mice; Microbiota; Microbiota (Symbiotic organisms); Neonates; Probiotics; Reverse transcription; Ribose; Risk factors; rRNA 16S; Scanning electron microscopy; Tight junctions; Transcriptomes; Tumor necrosis factor-α; Western blotting; China; United States > US; Antibiotics-induced intestinal flora; Tight junctions; Intestinal barrier function; Biofilm; Autoinducer-2; Lactobacillus rhamnosus GG; Butyric acid; Hydroxycarboxylic acid receptor 2
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-024-04991-5

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. 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. 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-α) 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. AI-2 promotes the colonization of LGG and biofilm formation to improve intestinal barrier function in an antibiotic-induced intestinal dysbiosis neonatal mouse model.