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深入了解玫瑰色双歧杆菌通过诱导抗炎反应缓解实验性结肠炎病理的机制。

Insights into Roseburia intestinalis which alleviates experimental colitis pathology by inducing anti-inflammatory responses.

机构信息

Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China.

出版信息

J Gastroenterol Hepatol. 2018 Oct;33(10):1751-1760. doi: 10.1111/jgh.14144. Epub 2018 May 7.

Abstract

BACKGROUND AND AIM

The study aims to elucidate the anti-inflammatory effect and mechanism of Roseburia intestinalis (R. intestinalis) in Crohn's disease (CD).

METHODS

16S-rRNA genome sequencing technique is used to detect the characteristics of intestinal microbiota in untreated CD patients and healthy controls. Then the study investigates the effects of R. intestinalis on disease activity index score, intestinal pathology, the differentiation of Treg cells, and the expressions of Thymic stromal lymphopoietin (TSLP), TGF-β and IL-10 by using TNBS colitis models. At the cellular level, the study uses LPS to stimulate Caco-2 cells to conduct inflammation models and then co-culture with R. intestinalis and detect changes of TSLP and TGF-β. The study then uses R. intestinalis to stimulate peripheral blood mononuclear cells, and the change of Treg cells was detected.

RESULTS

Genome sequencing of fecal samples from untreated CD patients (n = 10) revealed decreases in the abundance and diversity of intestinal microbiota, including R. intestinalis. Moreover, R. intestinalis reduced disease activity index scores, colon shortening, intestinal mucosal epithelial injury, and mucosal lymphocyte infiltration in a colitis mice model. It suppressed intestinal inflammation by increasing Treg cell numbers and expression of the anti-inflammatory cytokines TSLP, TGF-β, and interleukin-10 (P < 0.05). R. intestinalis also increased secretion of TSLP and TGF-β in lipopolysaccharide-treated Caco-2 cells.

CONCLUSION

These findings suggest that R. intestinalis suppresses CD pathogenesis by inducing anti-inflammatory responses.

摘要

背景与目的

本研究旨在阐明肠道罗斯伯里氏菌(R. intestinalis)在克罗恩病(CD)中的抗炎作用及机制。

方法

采用 16S-rRNA 基因组测序技术检测未经治疗的 CD 患者和健康对照者肠道微生物群的特征。然后,本研究通过 TNBS 结肠炎模型研究 R. intestinalis 对疾病活动指数评分、肠道病理学、Treg 细胞分化以及胸腺基质淋巴细胞生成素(TSLP)、TGF-β和 IL-10 的表达的影响。在细胞水平上,本研究使用 LPS 刺激 Caco-2 细胞构建炎症模型,然后与 R. intestinalis 共培养,检测 TSLP 和 TGF-β 的变化。然后,本研究使用 R. intestinalis 刺激外周血单核细胞,检测 Treg 细胞的变化。

结果

对未经治疗的 CD 患者(n=10)粪便样本的基因组测序显示,肠道微生物群的丰度和多样性下降,包括 R. intestinalis。此外,R. intestinalis 降低了结肠炎小鼠模型中的疾病活动指数评分、结肠缩短、肠黏膜上皮损伤和黏膜淋巴细胞浸润。它通过增加 Treg 细胞数量和抗炎细胞因子 TSLP、TGF-β 和白细胞介素-10 的表达来抑制肠道炎症(P<0.05)。R. intestinalis 还增加了脂多糖处理的 Caco-2 细胞中 TSLP 和 TGF-β 的分泌。

结论

这些发现表明 R. intestinalis 通过诱导抗炎反应抑制 CD 的发病机制。

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