Data_Sheet_1_Probiotics Modulate Mouse Gut Microbiota and Influence Intestinal Immune and Serotonergic Gene Expression in a Site-Specific Fashion.PDF

Probiotic microorganisms may benefit the host by influencing diverse physiological processes, whose nature and underlying mechanisms are still largely unexplored. Animal models are a unique tool to understand the complexity of the interactions between probiotic microorganisms, the intestinal microbiota, and the host. In this regard, in this pilot study, we compared the effects of 5-day administration of three different probiotic bacterial strains (Bifidobacterium bifidum MIMBb23sg, Lactobacillus helveticus MIMLh5, and Lacticaseibacillus paracasei DG) on three distinct murine intestinal sites (ileum, cecum, and colon). All probiotics preferentially colonized the cecum and colon. In addition, probiotics reduced in the ileum and increased in the cecum and colon the relative abundance of numerous bacterial taxonomic units. MIMBb23sg and DG increased the inducible nitric oxide synthase (iNOS) in the ileum, which is involved in epithelial homeostasis. In addition, MIMBb23sg upregulated cytokine IL-10 in the ileum and downregulated the cyclooxygenase COX-2 in the colon, suggesting an anti-inflammatory/regulatory activity. MIMBb23sg significantly affected the expression of the main gene involved in serotonin synthesis (TPH1) and the gene coding for the serotonin reuptake protein (SERT) in the ileum and colon, suggesting a potential propulsive effect toward the distal part of the gut, whereas the impact of MIMLh5 and DG on serotonergic genes suggested an effect toward motility control. The three probiotics decreased the expression of the permeability marker zonulin in gut distal sites. This preliminary in vivo study demonstrated the safety of the tested probiotic strains and their common ability to modulate the intestinal microbiota. The probiotics affected host gene expression in a strain-specific manner. Notably, the observed effects in the gut were site dependent. This study provides a rationale for investigating the effects of probiotics on the serotonergic system, which is a topic still widely unexplored.

益生菌（probiotic microorganisms）可通过调控多种生理过程使宿主获益，但其作用本质与潜在机制目前仍在很大程度上未被深入探索。动物模型是解析益生菌、肠道菌群与宿主间复杂互作关系的独特研究工具。有鉴于此，本先导研究对比了3株不同益生菌菌株（两歧双歧杆菌MIMBb23sg、瑞士乳杆菌MIMLh5以及副干酪乳杆菌Lacticaseibacillus paracasei DG）连续5天灌胃后，对小鼠3个不同肠道部位（回肠、盲肠与结肠）的影响。所有受试益生菌均优先在盲肠与结肠定植。此外，益生菌可使回肠内多种细菌分类单元的相对丰度降低，而在盲肠与结肠中使其相对丰度升高。MIMBb23sg与DG可上调回肠内诱导型一氧化氮合酶（inducible nitric oxide synthase, iNOS）的表达，该酶参与上皮细胞稳态维持。此外，MIMBb23sg可上调回肠内细胞因子IL-10的表达，并下调结肠中环氧化酶COX-2的表达，提示其具备抗炎/免疫调节活性。MIMBb23sg可显著影响回肠与结肠内参与5-羟色胺合成的关键基因（TPH1）以及编码5-羟色胺转运蛋白的基因（SERT）的表达，提示其可能对肠道远端产生促蠕动效应；而MIMLh5与DG对5-羟色胺能基因的影响则表明其可调控肠道运动。3株受试益生菌均可降低肠道远端部位中通透性标记物连蛋白（zonulin）的表达水平。本初步体内研究证实了受试益生菌菌株的安全性，以及它们共同具备的调控肠道菌群的能力。益生菌对宿主基因表达的调控作用呈现菌株特异性。值得注意的是，肠道内观测到的效应具有肠道部位依赖性。本研究为探究益生菌对5-羟色胺能系统的影响提供了理论依据，而该研究主题目前仍有待广泛探索。