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排斥导向分子b缺乏会导致小鼠肠道微生物群失调并增加肠道炎症易感性。

Repulsive Guidance Molecule b Deficiency Induces Gut Microbiota Dysbiosis and Increases the Susceptibility to Intestinal Inflammation in Mice.

作者信息

Shi Ying, Zhong Lu, Li Yuting, Chen Yanfang, Feng Shufen, Wang Min, Xia Yin, Tang Shaohui

机构信息

Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, China.

Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Tübingen, Tübingen, Germany.

出版信息

Front Microbiol. 2021 Apr 28;12:648915. doi: 10.3389/fmicb.2021.648915. eCollection 2021.

DOI:10.3389/fmicb.2021.648915
PMID:33995306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8113641/
Abstract

Imbalance of gut microbiota can induce or aggravate intestinal inflammation. To enhance our understanding of the molecular mechanisms of gut microbiota and inflammatory bowel disease (IBD), we studied the role of repulsive guidance molecule b (RGMb) in gut microbiota and colitis in mice. We generated Rgmb knockout mice and inducible Rgmb knockout mice and induced colitis using dextran sulfate sodium (DSS) in these mice. 16S ribosomal RNA (rRNA) high-throughput sequencing was performed to acquire the gut microbiota composition and abundance. We found that Rgmb deficiency significantly altered the diversity of gut microbiota and also induced dysbiosis. In sharp contrast to the balanced distribution of various bacteria in control mice, was almost exhausted in Rgmb-deficient mice under both basal and inflammatory conditions. Correlation analysis indicated that was negatively associated with inflammation in Rgmb-deficient mice with colitis. Similar results were obtained at the early inflammatory stage of colitis associated colon cancer (CAC). Taken together, our results reveal that Rgmb deficiency leads to dysbiosis of predominant gut microbiota under basal and inflammatory conditions. Rgmb-deficiency-mediated loss may render mice more susceptible to intestinal inflammation. Therefore, RGMb may be a novel potential target for reconstruction of the gut microbiota for the treatment of IBD.

摘要

肠道微生物群失衡可诱发或加重肠道炎症。为了加深我们对肠道微生物群与炎症性肠病(IBD)分子机制的理解,我们研究了排斥导向分子b(RGMb)在小鼠肠道微生物群和结肠炎中的作用。我们构建了Rgmb基因敲除小鼠和诱导型Rgmb基因敲除小鼠,并在这些小鼠中使用葡聚糖硫酸钠(DSS)诱导结肠炎。进行16S核糖体RNA(rRNA)高通量测序以获取肠道微生物群的组成和丰度。我们发现Rgmb缺陷显著改变了肠道微生物群的多样性,并诱导了生态失调。与对照小鼠中各种细菌的平衡分布形成鲜明对比的是,在基础和炎症条件下,Rgmb缺陷小鼠中的[某种细菌]几乎耗尽。相关性分析表明,在患有结肠炎的Rgmb缺陷小鼠中,[某种细菌]与炎症呈负相关。在结肠炎相关结肠癌(CAC)的早期炎症阶段也获得了类似的结果。综上所述,我们的结果表明,Rgmb缺陷在基础和炎症条件下导致主要肠道微生物群的生态失调。Rgmb缺陷介导的[某种细菌]缺失可能使小鼠更容易患肠道炎症。因此,RGMb可能是用于治疗IBD的肠道微生物群重建的新潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/4e63722d8104/fmicb-12-648915-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/33c255d0a572/fmicb-12-648915-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/59ec29b6cb90/fmicb-12-648915-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/f613d6d5019c/fmicb-12-648915-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/3bcf0ec4fcc9/fmicb-12-648915-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/4e63722d8104/fmicb-12-648915-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/33c255d0a572/fmicb-12-648915-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/59ec29b6cb90/fmicb-12-648915-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/f613d6d5019c/fmicb-12-648915-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/3bcf0ec4fcc9/fmicb-12-648915-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b73/8113641/4e63722d8104/fmicb-12-648915-g005.jpg

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