Jiang Zheng-Meng, Zeng Su-Ling, Huang Tian-Qing, Lin Yang, Wang Fang-Fang, Gao Xing-Jiao, Li Jing, Li Ping, Liu E-Hu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China.
Sci Bull (Beijing). 2023 Jul 30;68(14):1540-1555. doi: 10.1016/j.scib.2023.06.027. Epub 2023 Jun 28.
Gut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) is an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut microbiota to alleviate RA remains underexplored. To identify the critical gut microbial species and microbial metabolites associated with the RA-protective effects of SIN, the microbiota-dependent anti-RA effects of SIN were assessed by 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation. Metabolomics analysis, transcriptional analysis, and targeted bacteria/metabolites gavage were conducted to explore how SIN regulates gut microbiota to reduce the severity of RA. SIN could restore intestinal microbial balance by mainly modulating the abundance of Lactobacillus, and significantly relieve collagen-induced arthritis (CIA) symptoms in a gut microbiota-dependent manner. SIN significantly elevated microbial tryptophan metabolites indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA). Tryptophan metabolites supplementation could activate aryl hydrocarbon receptor (AhR) and regulate Th17/Treg balance in CIA rats. Intriguingly, SIN relieved the arthritis symptoms involving the enrichment of two beneficial anti-CIA Lactobacillus species, L. paracasei and L. casei by mono-colonization. The promising therapeutic function of SIN was mostly attributed to the activation of AhR by explicitly targeting the Lactobacillus and microbial tryptophan metabolites. The intestinal bacterium L. paracasei and L. casei may be used to reduce the severity of CIA.
肠道微生物群失调与类风湿性关节炎（RA）的发展有关。青藤碱（SIN）是一种用于治疗RA的有效免疫抑制和抗炎药物，但SIN如何调节肠道微生物群以减轻RA仍未得到充分研究。为了确定与SIN的RA保护作用相关的关键肠道微生物种类和微生物代谢产物，通过16S rRNA基因测序、抗生素治疗和粪便微生物群移植评估了SIN的微生物群依赖性抗RA作用。进行了代谢组学分析、转录分析和靶向细菌/代谢产物灌胃，以探讨SIN如何调节肠道微生物群以降低RA的严重程度。SIN主要通过调节乳酸杆菌的丰度来恢复肠道微生物平衡，并以肠道微生物群依赖性方式显著缓解胶原诱导的关节炎（CIA）症状。SIN显著提高了微生物色氨酸代谢产物吲哚-3-丙烯酸（IA）、吲哚-3-丙酸（IPA）和吲哚-3-乙酸（IAA）。补充色氨酸代谢产物可以激活芳烃受体（AhR）并调节CIA大鼠的Th17/Treg平衡。有趣的是，SIN通过单一定殖两种有益的抗CIA乳酸杆菌（副干酪乳杆菌和干酪乳杆菌）的富集来缓解关节炎症状。SIN有前景的治疗功能主要归因于通过明确靶向乳酸杆菌和微生物色氨酸代谢产物激活AhR。肠道细菌副干酪乳杆菌和干酪乳杆菌可用于降低CIA的严重程度。
