DataSheet_1_Dietary fiber may benefit chondrocyte activity maintenance.docx

The understanding of the link between the gut-bone axis is growing yearly, but the mechanisms involved are not yet clear. Our study analyzed the role of Sestrin2 (SESN2)pathway in the gut-bone axis. We established an osteoarthritis (OA) model in Sprague-Dawley (SD) rats using the anterior cruciate ligament transection (ACLT) procedure, followed by a dietary intervention with varying levels of dietary fiber content for 8 weeks. By 16S rRNA sequencing of the gut microbiota, we found that high dietary fiber (HDF) intake could significantly increase the Bacillota-dominant gut microbiota. Meanwhile, enzyme linked immunosorbent assay (ELISA) and histological analysis showed that intervention with HDF could reduce the degree of bone and joint lesions and inflammation. We hypothesize that HDF increased the dominant flora of Bacillota, up-regulated the expression of SESN2 in knee joint, and reduced gut permeability, thereby reducing systemic inflammatory response and the degree of bone and joint lesions. Therefore, the present study confirms that changes in gut microbiota induced by increased dietary fiber intake delayed the onset of OA by promoting up-regulation of SESN2 expression at the knee joint to maintain chondrocyte activity and reduce synovial inflammation.

人们对肠-骨轴（gut-bone axis）之间关联的认知逐年加深，但其中涉及的具体机制尚未完全阐明。本研究探讨了塞斯特林2（Sestrin2, SESN2）通路在肠-骨轴中的作用。我们通过前交叉韧带切断术（anterior cruciate ligament transection, ACLT）构建斯普拉格-道莱（Sprague-Dawley, SD）大鼠骨关节炎（OA）模型，随后给予不同膳食纤维水平的膳食干预，干预周期为8周。通过对肠道菌群进行16S核糖体RNA（16S rRNA）测序，我们发现高膳食纤维（HDF）摄入可显著富集以厚壁菌门（Bacillota）为优势菌的肠道菌群。同时，酶联免疫吸附测定（ELISA）与组织学分析结果显示，高膳食纤维干预可减轻骨关节病变与炎症程度。我们提出如下假设：高膳食纤维可通过富集厚壁菌门优势菌群，上调膝关节中SESN2的表达，并降低肠道通透性，进而减轻全身炎症反应与骨关节病变程度。因此，本研究证实：膳食纤维摄入增加诱导的肠道菌群改变，可通过促进膝关节SESN2表达上调以维持软骨细胞活性、减轻滑膜炎症，从而延缓骨关节炎的发作。