Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates microbiota dysbiosis in an experimental model of sepsis
Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates microbiota dysbiosis in an experimental model of sepsis
复制标题
鼠李糖乳杆菌 GG 治疗可改善脓毒症实验模型中的肠道通透性并调节微生物群失调
DOI：
10.3892/ijmm.2019.4050
复制
发表时间：
2019-03-01
影响因子：
5.4
通讯作者：
Yang, Yunmei
中科院分区：
文献类型：
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作者：
Chen, Lufang;Li, Hanyu;Yang, Yunmei
在重症监护病房患者中，“有益健康”的微生物减少和致病菌增加（一种称为生态失调的情况）被认为会诱发或加重败血症（肠道源性败血症）。口服益生菌在预防医院感染方面是有效的。然而，益生菌诱导的抗感染和抗败血症的机制仍有待探索。在本研究中，4周龄C57BL6小鼠在盲肠结扎穿刺（CLP）前4周口服鼠李糖乳杆菌GG （LGG）或生理盐水（对照组）。clp后24小时处死一部分小鼠，其余小鼠用于生存研究。收集回肠组织、血液和粪便样本。与未处理的小鼠相比，经LGG预处理的脓毒症小鼠的存活率明显提高。经lgg预处理的脓毒症小鼠炎症细胞因子水平降低。对照组败血性CLP+生理盐水小鼠结肠增殖和上皮紧密连接减少，结肠细胞凋亡增加。LGG预处理使大鼠结肠增殖、凋亡及紧密连接蛋白表达水平逆转至假手术组水平。LGG预处理提高了脓毒症小鼠肠道菌群的丰富度和多样性。主坐标分析聚类图显示，三组之间的微生物群结构存在显著的分离聚类。与能量消耗相关的细菌，包括拟杆菌门，与机会感染相关的细菌，包括变形杆菌门，葡萄球菌科和肠球菌科，脂多糖产生菌，包括肠杆菌科，兼性厌氧菌，如拟杆菌科和丹毒杆菌科，在脓毒症小鼠中增加。相比之下，与能量收集相关的细菌，包括厚壁菌门，肠道屏障功能调节剂，包括Akkermansia，肝功能调节剂，包括Coprococcus和Oscillospira，以及专门的厌氧菌，包括Prevotellaceae，在脓毒症小鼠中减少。经LGG预处理，败血症引起的菌群失调得到逆转。本研究结果阐明了LGG通过改善肠道通透性和调节微生物群失调来治疗脓毒症的潜在机制。
Decrease of 'health-benefiting' microbes and increase of pathogenic bacteria (a condition termed dysbiosis) in intensive care unit patients is considered to induce or aggravate sepsis (gut-origin sepsis). Orally administered probiotics have been effective in the prevention of nosocomial infections. However, the mechanisms of probiotic-induced anti-infection and anti-sepsis remain to be explored. In the present study, 4-week-old C57BL6 mice were orally administrated with Lactobacillus rhamnosus GG (LGG) or normal saline (control) 4 weeks prior to cecal ligation and puncture (CLP). A subset of the mice were sacrificed at 24 h post-CLP, and the others were used for survival studies. Ileum tissues, blood and fecal samples were collected. The survival rate of septic mice pretreated with LGG was significantly improved compared with untreated mice. The levels of inflammatory cytokines were reduced in LGG-pretreated septic mice. A decrease of colonic proliferation and epithelial tight junctions and an increase of colonic apoptosis were observed in control septic CLP+saline mice. LGG pretreatment reversed the colonic proliferation, apoptosis and expression of tight junction proteins to the levels of the sham group. LGG pretreatment improved the richness and diversity of intestinal microbiota in septic mice. The principal coordinates analysis clustering plots revealed a significant separate clustering in microbiota structure between three groups. Bacteria associated with energy consumption, including Bacteroidetes, with opportunistic infection, including Proteobacteria, Staphylococcaceae and Enterococcaceae, lipopolysaccharide producers, including Enterobacteriaceae, and facultative anaerobes, such as Bacteroidaceae and Erysipelotrichaceae, increased in septic mice. By contrast, bacteria associated with energy harvest, including Firmicutes, intestinal barrier function regulators, including Akkermansia, hepatic function regulators, including Coprococcus and Oscillospira, and obligate anaerobes, including Prevotellaceae, decreased in septic mice. With LGG pretreatment, the sepsis-induced microbiota dysbiosis was reversed. The present results elucidated the potential mechanism of LGG treatment in sepsis, by improving intestinal permeability and modulating microbiota dysbiosis.