In Vitro Characterization of Gut Microbiota-Derived Commensal Strains: Selection of Parabacteroides distasonis Strains Alleviating TNBS-Induced Colitis in Mice.

In Vitro Characterization of Gut Microbiota-Derived Commensal Strains: Selection of Parabacteroides distasonis Strains Alleviating TNBS-Induced Colitis in Mice.
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DOI:
10.3390/cells9092104
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发表时间:
2020-09-16
期刊:
影响因子:
6
通讯作者:
Grangette C
Grangette C
中科院分区:
生物学2区
文献类型:
--
作者:
Cuffaro B;Assohoun ALW;Boutillier D;Súkeníková L;Desramaut J;Boudebbouze S;Salomé-Desnoulez S;Hrdý J;Waligora-Dupriet AJ;Maguin E;Grangette C

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肠道微生物群组成和多样性的改变似乎在慢性疾病(包括炎症性肠病(IBD))的发展中发挥作用,导致肠道屏障破坏和诱导促炎免疫反应。这为使用新型健康促进细菌打开了大门。我们选择了五个Parabacteroides distasonis菌株分离自人类成人和新生儿肠道菌群。我们在体外评估了它们的免疫调节能力和增强肠道屏障的能力,并在急性结肠炎小鼠模型中表征了它们的体内保护作用。在体外有益的活动是高度菌株依赖性的:两个菌株表现出强大的抗炎潜力,并恢复肠道屏障,而第三个菌株恢复上皮屏障。虽然它们在体外胃条件下的存活率是可变的,但在细菌处理的动物的粪便中,吉氏原杆菌DNA的水平较高。在体外得到阳性评分的菌株显示出很强的拯救小鼠免于结肠炎的能力。我们进一步表明,两个菌株引发树突状细胞诱导调节性T淋巴细胞从幼稚的CD4+ T细胞。这项研究提供了关于肠道细菌功能的更好见解,以及设计能够靶向炎症性慢性疾病(如IBD)的活生物治疗药物的关键线索。
Alterations in the gut microbiota composition and diversity seem to play a role in the development of chronic diseases, including inflammatory bowel disease (IBD), leading to gut barrier disruption and induction of proinflammatory immune responses. This opens the door for the use of novel health-promoting bacteria. We selected five Parabacteroides distasonis strains isolated from human adult and neonates gut microbiota. We evaluated in vitro their immunomodulation capacities and their ability to reinforce the gut barrier and characterized in vivo their protective effects in an acute murine model of colitis. The in vitro beneficial activities were highly strain dependent: two strains exhibited a potent anti-inflammatory potential and restored the gut barrier while a third strain reinstated the epithelial barrier. While their survival to in vitro gastric conditions was variable, the levels of P. distasonis DNA were higher in the stools of bacteria-treated animals. The strains that were positively scored in vitro displayed a strong ability to rescue mice from colitis. We further showed that two strains primed dendritic cells to induce regulatory T lymphocytes from naïve CD4+ T cells. This study provides better insights on the functionality of commensal bacteria and crucial clues to design live biotherapeutics able to target inflammatory chronic diseases such as IBD.
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