Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis
Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis
复制标题
肠道丁酸盐代谢物种有助于类风湿关节炎中自身抗体的产生和骨侵蚀
DOI：
10.1126/sciadv.abm1511
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发表时间：
2022-02-01
期刊：
影响因子：
13.6
通讯作者：
Li, Zhanguo
中科院分区：
文献类型：
--
作者：
He, Jing;Chu, Yanan;Li, Zhanguo
类风湿性关节炎（RA）中肠道微生物组和代谢的致病和有益物种之间的不平衡仍然不清楚。在这里，使用基于猎枪的宏基因组测序的治疗初治患者队列和“准配对队列”的方法，我们观察到缺乏丁酸生产物种和绝大多数的丁酸消费者在RA患者。这些结局主要发生在ACPA阳性患者中，平均AUC为0.94。该组也在已确诊的RA中得到验证，关节畸形患者的AUC为0.986。此外，我们发现丁酸盐促进了T-conv，同时抑制了T-conv和破骨细胞，这是由于增强了HDAC表达的减少和促炎细胞因子基因的下调。饮食丁酸补充剂通过重新平衡T-FH细胞和T-FH以及减少抗体产生而在小鼠模型中赋予抗炎益处。这些发现揭示了丁酸代谢物质的关键作用，并表明丁酸为基础的治疗RA患者的潜力。
The imbalance between pathogenic and beneficial species of the intestinal microbiome and metabolism in rheumatoid arthritis (RA) remains unclarified. Here, using shotgun-based metagenome sequencing for a treatment-naive patient cohort and a "quasi-paired cohort" method, we observed a deficiency of butyrate-producing species and an overwhelming number of butyrate consumers in RA patients. These outcomes mainly occurred in patients with positive ACPA, with a mean AUC of 0.94. This panel was also validated in established RA with an AUC of 0.986 in those with joint deformity. In addition, we showed that butyrate promoted T-regs, while suppressing T-convs and osteoclasts, due to potentiation of the reduction in HDAC expression and down-regulation of proinflammatory cytokine genes. Dietary butyrate supplementation conferred anti-inflammatory benefits in a mouse model by rebalancing T-FH cells and T-regs, as well as reducing antibody production. These findings reveal the critical role of butyrate-metabolizing species and suggest the potential of butyrate-based therapies for RA patients.