You Ke, Yang Lianjun, Su Zhihai, Shen Jun, Fan Xinyang, Guo Yuanqing, Yuan Zhen, Lu Hai
Department of Spine Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519082, China.
Faculty of Health Sciences, University of Macau, Macau 999078, China.
Biomedicines. 2024 Dec 24;13(1):9. doi: 10.3390/biomedicines13010009.
Ankylosing spondylitis (AS) is a chronic inflammatory and autoimmune disease that primarily affects the sacroiliac joints and axial skeleton. While the exact pathogenetic mechanism of AS remains unclear, previous reports have highlighted the involvement of genetic factors, immune responses, and gut microbiota dysregulation in the development of this condition. Short-chain fatty acids (SCFAs), which are microbial fermentation products derived from sugar, protein, and dietary fibers, play a role in maintaining the intestinal barrier function and reducing inflammatory responses. The aim of this study was to investigate the therapeutic potential of butyric acid (BA), an important SCFA, in the treatment of AS. To evaluate the anti-inflammatory and anti-bone loss effects of BA, a murine AS model was established using proteoglycan and dimethyl dioctadecyl ammonium (DDA) adjuvants. Various techniques, including an enzyme-linked immunosorbent assay (ELISA), magnetic resonance imaging (MRI), micro-CT, histology, quantitative PCR (qPCR) for intestinal tight junction protein expression, and 16S rDNA sequencing to analyze gut microbiota abundance, were employed to assess the inflammation and bone health in the target tissues. The results indicated that BA demonstrated potential in alleviating the inflammatory response in the peripheral joints and the axial spine affected by AS, as evidenced by the reductions in inflammatory infiltration, synovial hyperplasia, and endplate erosion. Furthermore, BA was found to impact the intestinal barrier function positively. Notably, BA was associated with the downregulation of harmful inflammatory factors and the reversal of bone loss, suggesting its protective effects against AS. These beneficial effects were attributed to the modulation of gut microbiota, anti-inflammatory properties, and the maintenance of skeletal metabolic homeostasis. This study contributes new evidence supporting the relationship between gut microbiota and bone health.
强直性脊柱炎（AS）是一种慢性炎症性自身免疫性疾病，主要影响骶髂关节和中轴骨骼。虽然AS的确切发病机制尚不清楚，但先前的报告强调了遗传因素、免疫反应和肠道微生物群失调在该病发展中的作用。短链脂肪酸（SCFAs）是由糖、蛋白质和膳食纤维产生的微生物发酵产物，在维持肠道屏障功能和减轻炎症反应中发挥作用。本研究的目的是探讨重要的SCFA丁酸（BA）在治疗AS中的潜在作用。为了评估BA的抗炎和抗骨质流失作用，使用蛋白聚糖和二甲基二十八烷基铵（DDA）佐剂建立了小鼠AS模型。采用了多种技术，包括酶联免疫吸附测定（ELISA）、磁共振成像（MRI）、微型计算机断层扫描（micro-CT）、组织学、用于检测肠道紧密连接蛋白表达的定量聚合酶链反应（qPCR）以及用于分析肠道微生物群丰度的16S核糖体DNA测序，以评估靶组织中的炎症和骨骼健康状况。结果表明，BA在减轻受AS影响的外周关节和中轴脊柱的炎症反应方面具有潜力，炎症浸润、滑膜增生和终板侵蚀的减少证明了这一点。此外，发现BA对肠道屏障功能有积极影响。值得注意的是，BA与有害炎症因子的下调和骨质流失的逆转有关，表明其对AS具有保护作用。这些有益作用归因于肠道微生物群的调节、抗炎特性以及骨骼代谢稳态的维持。本研究为支持肠道微生物群与骨骼健康之间的关系提供了新的证据。
