The distinct effects of orally administered <i>Lactobacillus rhamnosus</i> GG and <i>Lactococcus lactis</i> subsp. <i>lactis</i> C59 on gene expression in the murine small intestine

The molecular mechanisms of strain-specific probiotic effects and the impact of the oral administration of probiotic strains on the host’s gene expression are not yet well understood. The aim of this study was to investigate the strain-specific effects of probiotic strain intake on gene expression in the murine small intestine. Two distinct strains of lactic acid bacteria, Lactobacillus rhamnosus GG (GG) and Lactococcus lactis subsp. lactis C59 (C59), were orally administered to BALB/c mice, daily for 2 weeks. The total RNA was isolated from the upper (including the duodenum) and lower (the terminal ileum) small intestine, and gene expression was assessed by microarray analysis. The data revealed (1) oral administration of C59 and GG markedly down-regulated the expression of genes encoding fibrinogen subunits and plasminogen in the upper small intestine; (2) administration of more than 1 × 107 CFU/day of GG changed the gene expression of the host ileum. (3) strain- and dose-related effects on various GO biological processes; and (4) enrichment for B cell-related Gene Ontology terms among up-regulated genes in the terminal ileum of mice administered the 1 × 109 CFU/day of GG. The distinct effects of GG and C59 on gene expression in the intact small intestine provide clues to understand how the health beneficial effects of specific strains of probiotic bacteria are mediated by interactions with intestinal cells.菌株特异性益生菌功效的分子机制，以及益生菌菌株经口给药后对宿主基因表达的影响，目前尚未得到充分阐明。本研究旨在探究摄入益生菌菌株后对小鼠小肠基因表达的菌株特异性影响。本研究选取两株不同的乳酸菌——鼠李糖乳杆菌GG（Lactobacillus rhamnosus GG, GG）与乳酸乳球菌乳酸亚种C59（Lactococcus lactis subsp. lactis C59, C59），每日经口给予BALB/c小鼠灌胃，持续2周。研究人员分别从小鼠小肠上段（含十二指肠）与下段（回肠末端）分离总RNA，并通过微阵列分析（microarray analysis）检测基因表达水平。实验数据显示：① 灌胃C59与GG均可显著下调小鼠小肠上段中编码纤维蛋白原亚基与纤溶酶原的基因表达；② 每日灌胃剂量超过1×10^7菌落形成单位（Colony-Forming Unit, CFU）的GG，可改变宿主回肠的基因表达模式；③ 不同菌株与给药剂量对各类基因本体（Gene Ontology, GO）生物学过程存在特异性影响；④ 每日灌胃1×10^9 CFU剂量GG的小鼠，其回肠末端上调基因中富集了与B细胞相关的基因本体术语。GG与C59对完整小肠基因表达的差异化影响，为阐明特定益生菌菌株通过与肠道细胞相互作用介导健康获益效应的分子机制提供了重要线索。