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GBP5 缺陷的慢性结肠炎小鼠模型中肠道微生物杜波西氏菌免疫反应减弱和丰度升高。

Diminished Immune Response and Elevated Abundance in Gut Microbe Dubosiella in Mouse Models of Chronic Colitis with GBP5 Deficiency.

机构信息

Medical College, Jiaying University, Meizhou 514031, China.

Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Biomolecules. 2024 Jul 20;14(7):873. doi: 10.3390/biom14070873.

DOI:10.3390/biom14070873
PMID:39062588
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11274912/
Abstract

Guanylate binding protein 5 (GBP5) is an emerging immune component that has been increasingly recognized for its involvement in autoimmune diseases, particularly inflammatory bowel disease (IBD). IBD is a complex disease involving inflammation of the gastrointestinal tract. Here, we explored the functional significance of GBP5 using knockout mice and wildtype mice exposed to dextran sulfate sodium (DSS) to generate chronic colitis model. We found that deficiency protected mice from DSS-induced chronic colitis. Transcriptome analysis of colon tissues showed reduced immune responses in knockout mice compared to those in corresponding wildtype mice. We further observed that after repeated DSS exposure, the gut microbiota was altered, both in wildtype mice and knockout mice; however, the gut microbiome health index was higher in the knockout mice. Notably, a probiotic murine commensal bacterium, , was predominantly enriched in these knockout mice. Our findings suggest that GBP5 plays an important role in promoting inflammation and dysbiosis in the intestine, the prevention of which might therefore be worth exploring in regards to IBD treatment.

摘要

鸟苷酸结合蛋白 5(GBP5)是一种新兴的免疫成分,其在自身免疫性疾病,特别是炎症性肠病(IBD)中的作用越来越受到关注。IBD 是一种涉及胃肠道炎症的复杂疾病。在这里,我们使用 GBP5 敲除小鼠和暴露于葡聚糖硫酸钠(DSS)以产生慢性结肠炎模型的野生型小鼠来探索 GBP5 的功能意义。我们发现 GBP5 缺乏可保护小鼠免受 DSS 诱导的慢性结肠炎。结肠组织的转录组分析显示,与相应的野生型小鼠相比,GBP5 敲除小鼠的免疫反应降低。我们进一步观察到,在反复 DSS 暴露后,无论是在野生型小鼠还是 GBP5 敲除小鼠中,肠道微生物群都发生了改变;然而,GBP5 敲除小鼠的肠道微生物组健康指数更高。值得注意的是,一种益生菌鼠共生菌 ,在这些敲除小鼠中主要富集。我们的研究结果表明,GBP5 在促进肠道炎症和失调中发挥重要作用,因此在 IBD 治疗方面值得探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/4830c3c07e2c/biomolecules-14-00873-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/67f4f25161ea/biomolecules-14-00873-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/49bf710e943e/biomolecules-14-00873-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/a9a71788eafe/biomolecules-14-00873-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/cf6a03dfce63/biomolecules-14-00873-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/4830c3c07e2c/biomolecules-14-00873-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/67f4f25161ea/biomolecules-14-00873-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/49bf710e943e/biomolecules-14-00873-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/a9a71788eafe/biomolecules-14-00873-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/cf6a03dfce63/biomolecules-14-00873-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9f/11274912/4830c3c07e2c/biomolecules-14-00873-g005.jpg

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