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类风湿性关节炎肠道微生物生物样本库揭示了与宿主炎症和自身免疫反应相关并产生影响的核心微生物物种。

The rheumatoid arthritis gut microbial biobank reveals core microbial species that associate and effect on host inflammation and autoimmune responses.

作者信息

Huang Hao-Jie, Liu Chang, Sun Xin-Wei, Wei Rui-Qi, Liu Ling-Wei, Chen Hao-Yu, Abdugheni Rashidin, Wang Chang-Yu, Wang Xiao-Meng, Jiang He, Niu Han-Yu, Feng Li-Juan, He Jia-Hui, Jiang Yu, Zhao Yan, Wang Yu-Lin, Shu Qiang, Bi Ming-Xia, Zhang Lei, Liu Bin, Liu Shuang-Jiang

机构信息

State Key Laboratory of Microbial Technology Shandong University Qingdao China.

Department of Rheumatology The Affiliated Hospital of Qingdao University Qingdao China.

出版信息

Imeta. 2024 Oct 3;3(5):e242. doi: 10.1002/imt2.242. eCollection 2024 Oct.

Abstract

Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular and culture-independent studies revealed RA patients harbored a core microbiome and had characteristic bacterial species, the lack of cultured bacterial strains had limited investigations on their functions. This study aimed to establish an RA-originated gut microbial biobank (RAGMB) that covers and further to correlates and validates core microbial species on clinically used and diagnostic inflammation and immune indices. We obtained 3200 bacterial isolates from fecal samples of 20 RA patients with seven improved and 11 traditional bacterial cultivation methods. These isolates were phylogenetically identified and selected for RAGMB. The RAGMB harbored 601 bacterial strains that represented 280 species (including 43 novel species) of seven bacterial phyla. The RAGMB covered 93.2% at species level of medium- and high-abundant (relative abundances ≥0.2%) RA gut microbes, and included four rare species of the phylum . The RA core gut microbiome was defined and composed of 20 bacterial species. Among these, and were two species that statistically and significantly correlated with clinically used diagnostic indices such as erythrocyte sedimentation rate (ESR) and IL-10. Thus, and were selected for experimental validation using DSS-treated and not DSS-treated mice model. Results demonstrated both and exacerbated host inflammatory responses, including shortened colon length and increased spleen weight, decreased IL-10 and increased IL-17A levels in plasma. Overall, we established the RAGMB, defined the RA core microbiome, correlated and demonstrated core microbial species effected on host inflammatory and immune responses. This work provides diverse gut microbial resources for future studies on RA etiology and potential new targets for new biomedical practices.

摘要

肠道微生物群失调与类风湿性关节炎(RA)有关,并影响疾病进展。尽管分子和非培养研究表明RA患者拥有核心微生物群且具有特征性细菌种类,但缺乏培养的细菌菌株限制了对其功能的研究。本研究旨在建立一个涵盖RA起源的肠道微生物生物样本库(RAGMB),并进一步将核心微生物种类与临床使用的诊断炎症和免疫指标进行关联和验证。我们采用7种改良和11种传统细菌培养方法,从20例RA患者的粪便样本中获得了3200株细菌分离株。对这些分离株进行系统发育鉴定,并选择纳入RAGMB。RAGMB包含601株细菌菌株,代表7个细菌门的280个物种(包括43个新物种)。RAGMB在中高丰度(相对丰度≥0.2%)的RA肠道微生物物种水平上覆盖了93.2%,并包括该门的4种稀有物种。定义了RA核心肠道微生物群,由20种细菌组成。其中,[具体物种1]和[具体物种2]这两种细菌与红细胞沉降率(ESR)和IL-10等临床使用的诊断指标在统计学上有显著相关性。因此,选择[具体物种1]和[具体物种2],使用经葡聚糖硫酸钠(DSS)处理和未经DSS处理的小鼠模型进行实验验证。结果表明,[具体物种1]和[具体物种2]均加剧了宿主炎症反应,包括结肠长度缩短、脾脏重量增加、血浆中IL-10水平降低和IL-17A水平升高。总体而言,我们建立了RAGMB,定义了RA核心微生物群,将核心微生物种类与宿主炎症和免疫反应进行了关联并证明了其作用。这项工作为未来RA病因学研究提供了多样的肠道微生物资源,并为新的生物医学实践提供了潜在的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed72/11487554/66199323a017/IMT2-3-e242-g005.jpg

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