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体外鉴定肠道共生菌菌株:筛选缓解三硝基苯磺酸诱导的结肠炎的菌株。

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

机构信息

Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Centre d'Infection et d'Immunité de Lille, 59000 Lille, France.

Institut Micalis, MIHA Team, Université Paris-Saclay, INRAE, AgroParisTech, 78350 Jouy-en-Josas, France.

出版信息

Cells. 2020 Sep 16;9(9):2104. doi: 10.3390/cells9092104.

Abstract

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 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 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.

摘要

肠道微生物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促炎免疫反应的诱导。这为新型有益菌的应用开辟了道路。我们从人类成人和新生儿肠道微生物群中分离出 5 株菌。我们评估了它们在体外的免疫调节能力及其增强肠道屏障的能力,并在急性结肠炎小鼠模型中体内表征了它们的保护作用。体外有益活性高度依赖于菌株:两种菌株表现出强大的抗炎潜力并恢复了肠道屏障,而第三种菌株恢复了上皮屏障。虽然它们在体外胃条件下的存活率不同,但在细菌处理动物的粪便中 DNA 水平更高。在体外评分较高的菌株具有从结肠炎中拯救小鼠的强大能力。我们进一步表明,两种菌株使树突状细胞能够从幼稚 CD4 T 细胞诱导调节性 T 淋巴细胞。这项研究为共生菌的功能提供了更好的见解,并为设计能够针对炎症性慢性疾病(如 IBD)的活体生物疗法提供了重要线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9bd/7565435/034bde64a276/cells-09-02104-g001.jpg

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