Stage-specific roles of microbial dysbiosis and metabolic disorders in rheumatoid arthritis.
Stage-specific roles of microbial dysbiosis and metabolic disorders in rheumatoid arthritis.
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微生物失调和代谢紊乱在类风湿性关节炎中的阶段特异性作用
DOI：
10.1136/ard-2022-222871
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发表时间：
2022-08-19
影响因子：
27.4
通讯作者：
中科院分区：
文献类型：
--
作者：
类风湿性关节炎（RA）是一种进行性疾病，包括四个阶段，其中肠道微生物群与发病机制有关。我们的目的是研究微生物生态失调和代谢紊乱在类风湿关节炎中的阶段性作用。我们研究了76例RA患者的粪便宏基因组和血浆代谢组的分期特征，这些患者根据2010年RA分类标准分为4个阶段（I-IV期），其中19例为骨关节炎患者，27例为健康人。为了验证细菌是否侵袭关节滑液，我们对来自四个RA分期的271例患者进行了16S rRNA基因测序、细菌分离和扫描电镜检查。首先，均匀拟杆菌和plebeius拟杆菌的消耗削弱了糖胺聚糖代谢（p<0.001），在四个阶段持续伤害关节软骨。其次，在II期和III期，大肠杆菌的升高增强了精氨酸琥珀基转移酶途径（p<0.001），这与类风湿因子的升高相关（p= 1.35×10-3），并可能导致骨质流失。第三，异常高水平的甲氧基乙酸（p= 1.28×10-8）和半胱氨酸-s -硫酸盐（p= 4.66×10-12）分别抑制II期成骨细胞和增强III期破骨细胞，促进骨侵蚀。第四，肠道通透性的持续增加可能导致IV期肠道微生物侵入关节滑液。临床微生物干预应考虑RA期，此时微生物生态失调和代谢紊乱表现出不同的模式，并发挥阶段性作用。我们的工作提供了从阶段角度理解肠关节轴的新视角，为RA的预后和治疗开辟了新的途径。
Rheumatoid arthritis (RA) is a progressive disease including four stages, where gut microbiome is associated with pathogenesis. We aimed to investigate stage-specific roles of microbial dysbiosis and metabolic disorders in RA. We investigated stage-based profiles of faecal metagenome and plasma metabolome of 76 individuals with RA grouped into four stages (stages I–IV) according to 2010 RA classification criteria, 19 individuals with osteroarthritis and 27 healthy individuals. To verify bacterial invasion of joint synovial fluid, 16S rRNA gene sequencing, bacterial isolation and scanning electron microscopy were conducted on another validation cohort of 271 patients from four RA stages. First, depletion of Bacteroides uniformis and Bacteroides plebeius weakened glycosaminoglycan metabolism (p<0.001), continuously hurting articular cartilage across four stages. Second, elevation of Escherichia coli enhanced arginine succinyltransferase pathway in the stage II and stage III (p<0.001), which was correlated with the increase of the rheumatoid factor (p=1.35×10–3) and could induce bone loss. Third, abnormally high levels of methoxyacetic acid (p=1.28×10–8) and cysteine-S-sulfate (p=4.66×10–12) inhibited osteoblasts in the stage II and enhanced osteoclasts in the stage III, respectively, promoting bone erosion. Fourth, continuous increase of gut permeability may induce gut microbial invasion of the joint synovial fluid in the stage IV. Clinical microbial intervention should consider the RA stage, where microbial dysbiosis and metabolic disorders present distinct patterns and played stage-specific roles. Our work provides a new insight in understanding gut–joint axis from a perspective of stages, which opens up new avenues for RA prognosis and therapy.
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DOI：
10.1016/s0272-0590(82)80039-0
发表时间：
1982-07-01
期刊：
Fundamental and applied toxicology : official journal of the Society of Toxicology
影响因子：
--
作者：
Miller, R R;Carreon, R E;McKenna, M J
通讯作者：
McKenna, M J
影响因子：
7
作者：
Severmann AC;Jochmann K;Feller K;Bachvarova V;Piombo V;Stange R;Holzer T;Brachvogel B;Esko J;Pap T;Hoffmann D;Vortkamp A
通讯作者：
Vortkamp A
影响因子：
5.9
作者：
Carr AC;Maggini S
通讯作者：
Maggini S
影响因子：
4.9
作者：
Shamdani S;Chantepie S;Flageollet C;Henni-Chebra N;Jouan Y;Eymard F;Hay E;Cohen-Solal M;Papy-Garcia D;Chevalier X;Albanese P
通讯作者：
Albanese P
影响因子：
27.4
作者：
ABRAMS, E;SANDSON, J
通讯作者：
SANDSON, J