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小肠衍生的普雷沃氏菌模拟生物作为治疗剂。

Small intestinal derived Prevotella histicola simulates biologic as a therapeutic agent.

机构信息

Department of Immunology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.

Chobani LLC, North Brunswick, NJ, USA.

出版信息

Sci Rep. 2024 Nov 25;14(1):29217. doi: 10.1038/s41598-024-80635-4.

DOI:10.1038/s41598-024-80635-4
PMID:39587228
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11589831/
Abstract

A role of gut microbiome in pathogenesis as well as response to treatment is documented in rheumatoid arthritis. Using a novel duodenal derived Prevotella histicola strain MCI 001, we have shown that it suppresses disease progression in a collagen-induced arthritis (CIA), a model for rheumatoid arthritis (RA) using humanized mice expressing HLA-DQ8 gene in the absence of endogenous class II genes. Here we compared efficacy of P. histicola MCI 001 with tumor necrosis factor inhibitor (TNFi) for treating arthritis. DQ8 arthritic mice treated with P. histicola by oral gavage or TNFi, were compared for disease onset, incidence and severity. We demonstrate that oral treatment with P. histicola mimics treatment with TNFi in arthritic DQ8 mice. A pangenome comparison of our P. histicola MCI 001 with its closest available neighbors depicted it as a novel strain with unique gene sequences that may contribute to immune modulatory effects. Notably, it possesses a unique sequence of an outer membrane protein, BtuB, which is involved in vitamin B12 transport. Our data indicate that P. histicola MC001 is an attractive candidate to prevent the progression of disease in RA patients with ongoing disease.

摘要

肠道微生物群在类风湿关节炎的发病机制以及对治疗的反应中起着重要作用。我们使用一种新型的十二指肠衍生普雷沃氏菌(Prevotella histicola)菌株 MCI 001,表明它可以抑制胶原诱导关节炎(CIA)模型中的疾病进展,该模型使用在缺乏内源性 II 类基因的情况下表达 HLA-DQ8 基因的人源化小鼠。在这里,我们比较了普雷沃氏菌 MCI 001 与肿瘤坏死因子抑制剂(TNFi)治疗关节炎的疗效。通过口服灌胃或 TNFi 治疗 DQ8 关节炎小鼠,比较其发病、发病率和严重程度。我们证明,口服普雷沃氏菌 MCI 001 治疗可模拟 TNFi 治疗 DQ8 关节炎小鼠。我们对 MCI 001 进行了全基因组比较,发现它与最接近的现有菌株存在差异,具有独特的基因序列,可能有助于免疫调节作用。值得注意的是,它具有独特的外膜蛋白 BtuB 序列,该序列参与维生素 B12 转运。我们的数据表明,普雷沃氏菌 MCI 001 是一种有吸引力的候选药物,可以预防正在发病的 RA 患者疾病的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9902/11589831/5e1c8803a223/41598_2024_80635_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9902/11589831/86f60b8ac18e/41598_2024_80635_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9902/11589831/a326775b8eee/41598_2024_80635_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9902/11589831/5e1c8803a223/41598_2024_80635_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9902/11589831/86f60b8ac18e/41598_2024_80635_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9902/11589831/a326775b8eee/41598_2024_80635_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9902/11589831/5e1c8803a223/41598_2024_80635_Fig3_HTML.jpg

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