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益生菌粪肠球菌 Symbioflor 1 通过细菌拮抗和调节 Th1-Th2 改善孕鼠的病原体诱导流产。

Probiotic Enterococcus faecalis Symbioflor 1 ameliorates pathobiont-induced miscarriage through bacterial antagonism and Th1-Th2 modulation in pregnant mice.

机构信息

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, Jiangxi, China.

Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.

出版信息

Appl Microbiol Biotechnol. 2020 Jun;104(12):5493-5504. doi: 10.1007/s00253-020-10609-9. Epub 2020 Apr 20.

DOI:10.1007/s00253-020-10609-9
PMID:32314005
Abstract

The bacterium-bacterium interaction between pathogenic and probiotic Enterococcus as well as the bacterium-host interaction between Enterococcus and intestinal epithelium has drawn increasing attentions, but the influence of those interactions on host pregnancy remains largely unexplored. In the present study, we evaluated the effects of probiotic E. faecalis Symbioflor 1 or/and pathogenic E. faecalis OG1RF on the miscarriage of pregnant mice. Using in vitro assays of competition and exclusion and displacement, antagonistic property of E. faecalis Symbioflor 1 against E. faecalis OG1RF was observed, and the former inhibited the translocation of the later in vivo. The rate of miscarriage induced by E. faecalis OG1RF challenge was significantly reduced by 28% with E. faecalis Symbioflor 1 intervention; and the tissue integrity of ileum, colon, uterus, and placenta and placental blood cell density in pregnant mice were drastically improved by such probiotic intervention. Compared with the controls, probiotic intervention significantly upregulated the level of IL-10 and TGF-β, downregulated levels of IFN-γ, and increased progesterone level that reversed the trend of being Th1 predominance state reported for adverse pregnancy outcome at early pregnancy stage. In conclusion, E. faecalis Symbioflor 1 decreased the translocation of E. faecalis OG1RF, prevented pathogen-induced tissue damage, and changed Th1-Th2 homeostasis toward Th2 predominance during early pregnancy resulting in decreased miscarriage. KEY POINTS: •The mechanism of how probiotic E. faecalis Symbioflor 1 improves pregnancy of mice • Influence of interactions of pathogenic and probiotic Enterococcus on host pregnancy • E. faecalis Symbioflor 1 change Th1-Th2 homeostasis toward Th2 predominance.

摘要

肠球菌属细菌-细菌的相互作用,以及肠球菌属细菌与肠道上皮细胞的细菌-宿主相互作用,引起了越来越多的关注,但这些相互作用对宿主妊娠的影响在很大程度上仍未得到探索。在本研究中,我们评估了益生菌屎肠球菌 Symbioflor 1 和/或致病菌屎肠球菌 OG1RF 对怀孕小鼠流产的影响。通过竞争和排除以及置换的体外试验,观察到屎肠球菌 Symbioflor 1 对屎肠球菌 OG1RF 的拮抗特性,并且前者在体内抑制了后者的易位。屎肠球菌 OG1RF 攻毒引起的流产率通过屎肠球菌 Symbioflor 1 干预降低了 28%;并且益生菌干预极大地改善了怀孕小鼠回肠、结肠、子宫和胎盘的组织完整性以及胎盘血细胞密度。与对照组相比,益生菌干预显著上调了 IL-10 和 TGF-β 的水平,下调了 IFN-γ 的水平,并增加了孕激素水平,这逆转了早孕阶段不良妊娠结局报告的 Th1 优势状态的趋势。总之,屎肠球菌 Symbioflor 1 减少了屎肠球菌 OG1RF 的易位,防止了病原体引起的组织损伤,并在早孕期间改变了 Th1-Th2 平衡向 Th2 优势,从而降低了流产率。关键点:•益生菌屎肠球菌 Symbioflor 1 改善小鼠妊娠的机制•致病菌和益生菌肠球菌相互作用对宿主妊娠的影响•屎肠球菌 Symbioflor 1 改变 Th1-Th2 平衡向 Th2 优势。

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