生物技术通报2024，Vol.40Issue(3)：286-295,10.DOI:10.13560/j.cnki.biotech.bull.1985.2023-0840
脆弱拟杆菌六型分泌系统对肠道屏障的影响及机制
Influence and Mechanism of Bacteroides fragilis Type VI Secretory System on the Intestinal Barrier
摘要
Abstract
[Objective]To investigate the effect and mechanism of Bacteroides fragilis type Ⅵ protein secretion system(T6SS)on the intestinal barrier.[Method]Suicide vector was used to construct B.fragilis T6SS mutant strain.The dextran sulfate sodium(DSS)salt-induced colitis mouse model was constructed,and supplemented mice with PBS,B.fragilis WT,and B.fragilis ΔT6SS,respectively.The disease characters and intestinal barrier integrity were compared among the three groups.Quantitative PCR and immunohistochemistry were used to detect the expressions of tight junction proteins.Untargeted metabolomics was used to compare gut differential metabolites in each group of mice.[Result]The deletion of T6SS did not affect bio-viability of B.fragilis.B.fragilis WT showed the improvements in body weight loss and colon length compared to PBS controls,demonstrating the protection to DSS-induced colitis;while this protection was lost with the absence of T6SS.The fluorescein isothiocyanate dextran concentration in the mouse serum and histological examination in intestinal pathological sections indicated that B.fragilis T6SS improved the integrity of the intestinal barrier in mice.T6SS mutation affected intestinal tight junction protein expression,confirmed by quantitative PCR and immunohistochemistry.Untargeted metabolomics analysis revealed 96 up-regulated differentially expressed metabolites in the B.fragilis WT group,compared to the B.fragilis ΔT6SS group,with multiple metabolites enriched in cholinergic synaptic metabolism and glycerophospholipid metabolism-related pathways.[Conclusion]B.fragilis T6SS alters intestinal metabolome and increases the expression of tight junction protein in intestinal cells,thus improving the permeability of intestinal barrier,being involved in the protection of B.fragilis to the intestinal barrier.关键词
肠道菌群/六型分泌系统/肠道屏障/肠道炎症/代谢产物Key words
microbiota/T6SS/intestinal barrier/intestinal inflammation/metabolites引用本文复制引用
雷棋怡,徐杨,李鹏飞..脆弱拟杆菌六型分泌系统对肠道屏障的影响及机制[J].生物技术通报,2024,40(3):286-295,10.基金项目
国家自然科学基金项目(82100231),江苏省双创博士项目(JSSCBS20211562),姑苏卫生人才科研项目(S2022021) （82100231）
