Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Int J Mol Med. 2019 Mar;43(3):1139-1148. doi: 10.3892/ijmm.2019.4050. Epub 2019 Jan 7.
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.
在重症监护病房患者中，“有益健康”的微生物减少和致病性细菌（称为生态失调）增加被认为会诱发或加重脓毒症（肠道来源的脓毒症）。口服益生菌已被证明可有效预防医院获得性感染。然而，益生菌诱导的抗感染和抗脓毒症的机制仍有待探索。在本研究中，4 周龄的 C57BL6 小鼠在盲肠结扎和穿刺（CLP）前 4 周口服鼠李糖乳杆菌 GG（LGG）或生理盐水（对照）。一部分小鼠在 CLP 后 24 小时处死，其余用于生存研究。收集回肠组织、血液和粪便样本。与未治疗的小鼠相比，用 LGG 预处理的脓毒症小鼠的存活率显著提高。LGG 预处理的脓毒症小鼠的炎症细胞因子水平降低。在对照脓毒症 CLP+盐水小鼠中，观察到结肠增殖和上皮紧密连接减少，结肠凋亡增加。LGG 预处理逆转了结肠增殖、凋亡和紧密连接蛋白的表达，使其达到假手术组的水平。LGG 预处理改善了脓毒症小鼠肠道微生物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，包括变形菌门、葡萄球菌科和肠球菌科，内毒素产生菌，包括肠杆菌科，以及兼性厌氧菌，如拟杆菌科和真杆菌科，在脓毒症小鼠中增加。相比之下，与能量收获相关的细菌，包括厚壁菌门，肠道屏障功能调节剂，包括阿克曼氏菌，肝脏功能调节剂，包括粪球菌和颤螺菌，以及专性厌氧菌，包括普雷沃氏菌科，在脓毒症小鼠中减少。用 LGG 预处理后，脓毒症引起的微生物失调得到逆转。本研究结果阐明了 LGG 治疗脓毒症的潜在机制，即改善肠道通透性和调节微生物失调。
