Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China; Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510000, China.
Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China.
Cell Metab. 2024 Nov 5;36(11):2367-2382.e5. doi: 10.1016/j.cmet.2024.08.007. Epub 2024 Sep 10.
Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized by inflammatory activity with distinct rhythmic fluctuations. However, the precise mechanisms governing these inflammatory rhythms remain elusive. Here, we explore the interaction between dietary patterns, gut microbiota diurnal oscillations, and the rhythmicity of RA in both collagen-induced arthritis (CIA) mice and patients with RA and highlight the significance of dietary timing in modulating RA inflammatory rhythms linked to gut microbiota. Specifically, we discovered that Parabacteroides distasonis (P. distasonis) uses β-glucosidase (β-GC) to release glycitein (GLY) from the diet in response to daily nutritional cues, influencing RA inflammatory rhythms dependent on the sirtuin 5-nuclear factor-κB (SIRT5-NF-κB) axis. Notably, we validated the daily fluctuations of P. distasonis-β-GC-GLY in patients with RA through continuous sampling across day-night cycles. These findings underscore the crucial role of dietary timing in RA rhythmicity and propose potential clinical implications for novel therapeutic strategies to alleviate arthritis.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，其特征是炎症活动具有明显的节律性波动。然而，调节这些炎症节律的确切机制仍难以捉摸。在这里，我们探讨了饮食模式、肠道微生物昼夜节律波动与胶原诱导性关节炎（CIA）小鼠和 RA 患者 RA 节律性之间的相互作用，并强调了饮食时间安排在调节与肠道微生物相关的 RA 炎症节律中的重要性。具体来说，我们发现 Parabacteroides distasonis（P. distasonis）利用β-葡萄糖苷酶（β-GC）根据每日营养线索从饮食中释放大豆苷元（GLY），影响依赖 SIRT5-NF-κB 轴的 RA 炎症节律。值得注意的是，我们通过在日夜周期内进行连续采样，在 RA 患者中验证了 P. distasonis-β-GC-GLY 的每日波动。这些发现强调了饮食时间安排在 RA 节律性中的关键作用，并为缓解关节炎的新型治疗策略提出了潜在的临床意义。
