Brun Paola, Scarpa Melania, Marchiori Chiara, Sarasin Gloria, Caputi Valentina, Porzionato Andrea, Giron Maria Cecilia, Palù Giorgio, Castagliuolo Ignazio
Department of Molecular Medicine, University of Padova, Padova, Italy.
Department of Neurosciences, University of Padova, Padova, Italy.
PLoS One. 2017 Jul 21;12(7):e0181863. doi: 10.1371/journal.pone.0181863. eCollection 2017.
We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure.
Mice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S. boulardii (107 CFU/day) or vehicle. After 4 weeks the following were determined: a) intestinal motility using fluorescein-isothiocyanate dextran distribution in the gut, fecal pellet expulsion, stool water content, and distal colonic transit of glass beads; b) integrity of the enteric nervous system (ENS) by immunohistochemistry on ileal whole-mount preparations and western blot of protein lysates from ileal longitudinal muscle and myenteric plexus; c) isometric muscle tension with electric field and pharmacological (carbachol) stimulation of ileal segments; and d) intestinal inflammation by levels of tumor necrosis factor α, interleukin(IL)-1β, IL-10 and IL-4.
S. boulardii CNCM I-745 improved HSV-1 induced intestinal dysmotility and alteration of intestinal transit observed ten weeks after IG inoculum of the virus. Also, the probiotic yeast ameliorated the structural alterations of the ENS induced by HSV-1 (i.e., reduced peripherin immunoreactivity and expression, increased glial S100β protein immunoreactivity and neuronal nitric oxide synthase level, reduced substance P-positive fibers). Moreover, S. boulardii CNCM I-745 diminished the production of HSV-1 associated pro-inflammatory cytokines in the myenteric plexus and increased levels of anti-inflammatory interleukins.
S. boulardii CNCM I-745 ameliorated gastrointestinal neuromuscular anomalies in a mouse model of gut dysfunctions typically observed with irritable bowel syndrome.
我们评估了布拉酵母菌CNCM I-745对单纯疱疹病毒1型（HSV-1）暴露引发的胃肠道运动功能障碍的肠易激综合征（IBS）型小鼠模型中肠道神经肌肉异常的影响。
在0周时给小鼠鼻内接种HSV-1（102 空斑形成单位）或赋形剂，4周后通过胃内（IG）途径（108 空斑形成单位）接种。IG接种6周后，将小鼠随机分配接受口服灌胃给予布拉酵母菌（107 菌落形成单位/天）或赋形剂。4周后测定以下指标：a）使用异硫氰酸荧光素葡聚糖在肠道中的分布、粪便颗粒排出、粪便含水量以及玻璃珠在远端结肠的转运来评估肠道运动；b）通过对回肠整装标本进行免疫组织化学以及对回肠纵肌和肌间神经丛的蛋白质裂解物进行蛋白质印迹来评估肠神经系统（ENS）的完整性；c）用电场和药理学（卡巴胆碱）刺激回肠段来测定等长肌肉张力；d）通过肿瘤坏死因子α、白细胞介素（IL）-1β、IL-10和IL-4的水平评估肠道炎症。
布拉酵母菌CNCM I-745改善了病毒IG接种10周后观察到的HSV-1诱导的肠道运动障碍和肠道转运改变。此外，益生菌酵母改善了HSV-1诱导的ENS结构改变（即降低外周蛋白免疫反应性和表达、增加胶质细胞S100β蛋白免疫反应性和神经元型一氧化氮合酶水平、减少P物质阳性纤维）。而且，布拉酵母菌CNCM I-745减少了肌间神经丛中与HSV-1相关的促炎细胞因子的产生并增加了抗炎白细胞介素的水平。
布拉酵母菌CNCM I-745改善了肠道功能障碍小鼠模型中通常在肠易激综合征中观察到的胃肠道神经肌肉异常。
