State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Gut. 2023 Sep;72(9):1664-1677. doi: 10.1136/gutjnl-2022-327756. Epub 2023 Jan 5.
Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA.
Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal in RA. The effects of -derived microbial metabolites on the differentiation of CD4 T cells and macrophage polarisation were also investigated.
The relative abundance of in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of .
and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.
肠道微生物失调与类风湿关节炎（RA）的发病机制密切相关。我们旨在确定潜在的益生菌肠道微生物，以改善 RA 的发展。
通过 16S rDNA 细菌基因测序和鸟枪法宏基因组学研究 RA 患者和健康个体的微生物组谱。使用胶原诱导性关节炎小鼠和 TNF-α转基因小鼠来评估肠道共生菌在 RA 中的作用。还研究了 -衍生的微生物代谢产物对 CD4 T 细胞分化和巨噬细胞极化的影响。
RA 新发病例和有病史的 RA 患者中 的相对丰度下调，这种减少与疾病活动评分-28（DAS28）呈负相关。用活菌（LPD）口服治疗关节炎小鼠可显著改善 RA 发病机制。LPD 衍生的石胆酸（LCA）、脱氧胆酸（DCA）、异石胆酸（isoLCA）和 3-氧代石胆酸（3-oxoLCA）对 RA 的治疗具有相似且协同的作用。除了直接抑制 Th17 细胞的分化外，3-oxoLCA 和 isoLCA 被鉴定为 TGR5 激动剂，促进巨噬细胞的 M2 极化。胆汁盐水解酶的特异性合成抑制剂通过减少这四种胆汁酸的产生，减弱了 LPD 的抗关节炎作用。天然产物人参皂苷 Rg2 通过促进 的生长表现出其抗 RA 作用。
和人参皂苷 Rg2 可能代表治疗 RA 的益生菌和益生元制剂。
