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从体外到体内:肠道疾病中候选益生菌菌株选择与表征的合理流程图

From In Vitro to In Vivo: A Rational Flowchart for the Selection and Characterization of Candidate Probiotic Strains in Intestinal Disorders.

作者信息

Maillard Flore, Meynier Maëva, Mondot Stanislas, Pepke Frederic, Galbert Chloé, Torres Maravilla Edgar, Kropp Camille, Sokol Harry, Carvalho Frédéric Antonio, Jacouton Elsa, Holowacz Sophie, Langella Philippe, Chain Florian, Martín Rebeca

机构信息

INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, 78350 Jouy-en-Josas, France.

PiLeJe Laboratoire, 75015 Paris, France.

出版信息

Microorganisms. 2023 Mar 30;11(4):906. doi: 10.3390/microorganisms11040906.

Abstract

Experimental and clinical evidence has demonstrated the potential of probiotic strains in the prevention or treatment of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). However, there is little data on what the methodology leading to the identification of such strains should be. In this work, we propose a new flowchart to identify strains with probiotic potential for the management of IBS and IBD, which we tested on a collection of 39 lactic acid bacteria and Bifidobacteria strains. This flowchart included in vitro tests of immunomodulatory properties on intestinal and peripheral blood mononuclear cells (PBMCs), assessment of the barrier-strengthening effect by measuring transepithelial electric resistance (TEER) and quantification of short-chain fatty acids (SCFAs) and aryl hydrocarbon receptor (AhR) agonists produced by the strains. The in vitro results were then combined in a principal component analysis (PCA) to identify strains associated with an anti-inflammatory profile. To validate our flowchart, we tested the two most promising strains identified in the PCA in mouse models of post-infectious IBS or chemically induced colitis to mimic IBD. Our results show that this screening strategy allows the identification of strains with potential beneficial effects on colonic inflammation and colonic hypersensitivity.

摘要

实验和临床证据已证明益生菌菌株在预防或治疗炎症性肠病(IBD)和肠易激综合征(IBS)方面的潜力。然而,关于鉴定此类菌株的方法的数据却很少。在这项工作中,我们提出了一种新的流程图,用于鉴定具有益生菌潜力的菌株,以管理IBS和IBD,我们在一组39株乳酸菌和双歧杆菌菌株上对其进行了测试。该流程图包括对肠道和外周血单核细胞(PBMC)的免疫调节特性的体外测试、通过测量跨上皮电阻(TEER)评估屏障增强效果以及对菌株产生的短链脂肪酸(SCFA)和芳烃受体(AhR)激动剂进行定量。然后,将体外结果结合到主成分分析(PCA)中,以鉴定与抗炎谱相关的菌株。为了验证我们的流程图,我们在感染后IBS或化学诱导结肠炎的小鼠模型中测试了在PCA中鉴定出的最有前景的两种菌株,以模拟IBD。我们的结果表明,这种筛选策略能够鉴定出对结肠炎症和结肠超敏反应具有潜在有益作用的菌株。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162a/10142325/2802a969fe44/microorganisms-11-00906-g001.jpg

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