Department of Orthopaedics, Hunan Provincial People's Hospital, Changsha, Hunan, 410001, China.
Department of Orthopaedics, Hunan Provincial People's Hospital, Changsha, Hunan, 410001, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Feb;1870(2):166972. doi: 10.1016/j.bbadis.2023.166972. Epub 2023 Nov 26.
The imbalance in gut microbiota triggers an inflammatory response that spreads from the gut to the discs and is associated with lumbar disc herniation (LDH). In this study, we investigated the mechanism of palmitic acid (PA) and trans-4-hydroxy-3-methoxycinnamic acid (THMC) on microbiota, metabolic homeostasis, and autophagy after LDH. The LDH rat model was established by puncturing the exposed intervertebral disc. 16S rDNA was used to assess the gut microbiome composition. The microbial metabolites were analyzed by UPLC-MS. The mechanism of PA and THMC in LDH was explored by fecal microbiota transplantation (FMT). We found that Yaobishu, PA, THMC, and the positive control drug Celebrex attenuated intervertebral disc damage in LDH rats and downregulated TRPV1, IL-1β, and IL-18 expression. In addition, Yaobishu reduced Oscillospirales and Ruminococcaceae abundances after LDH. PA increased Bacilli's abundance while decreasing Negativicutes and Ruminococcaceae abundances. Metabolomics showed that Yaobishu increased 2-hexanone, methyl isobutyl ketone, 2-methylpentan-3-one, and nonadecanoic acid levels but decreased pantetheine and urocanate levels. PA and THMC reduced uridine and urocanate levels. Yaobishu, PA, and THMC activated autophagy and the Wnt/β-catenin pathway in LDH rats. Moreover, antibiotics abrogated these effects. FMT-PA and FMT-THMC activated autophagy and decreased IL-1β, IL-18, Wnt1, β-catenin, and TRPV1 expression. FMT-PA and FMT-THMC partially reversed the effects of 3-MA. Taken together, our data suggest that Yaobishu, PA, and THMC relieve inflammation and pain by remodeling the gut microbiota and restoring metabolic homeostasis after LDH to activate autophagy and the Wnt/β-catenin pathway, which provide a new therapeutic target for LDH in the clinic.
肠道微生物失衡引发炎症反应，从肠道扩散到椎间盘，与腰椎间盘突出症（LDH）有关。在这项研究中，我们研究了棕榈酸（PA）和反式-4-羟基-3-甲氧基肉桂酸（THMC）对 LDH 后微生物群、代谢稳态和自噬的作用机制。通过穿刺暴露的椎间盘建立 LDH 大鼠模型。使用 16S rDNA 评估肠道微生物组组成。通过 UPLC-MS 分析微生物代谢产物。通过粪便微生物群移植（FMT）探索 PA 和 THMC 在 LDH 中的作用机制。我们发现，瑶宝舒、PA、THMC 和阳性对照药物塞来昔布减轻了 LDH 大鼠的椎间盘损伤，并下调了 TRPV1、IL-1β 和 IL-18 的表达。此外，瑶宝舒降低了 LDH 后 Oscillospirales 和 Ruminococcaceae 的丰度。PA 增加了 Bacilli 的丰度，同时降低了 Negativicutes 和 Ruminococcaceae 的丰度。代谢组学显示，瑶宝舒增加了 2-己酮、甲基异丁基酮、2-甲基戊烷-3-酮和十九烷酸的水平，但降低了 pantetheine 和尿刊酸的水平。PA 和 THMC 降低了尿苷和尿刊酸的水平。瑶宝舒、PA 和 THMC 在 LDH 大鼠中激活了自噬和 Wnt/β-连环蛋白通路。此外，抗生素消除了这些作用。FMT-PA 和 FMT-THMC 激活了自噬，降低了 IL-1β、IL-18、Wnt1、β-连环蛋白和 TRPV1 的表达。FMT-PA 和 FMT-THMC 部分逆转了 3-MA 的作用。综上所述，我们的数据表明，瑶宝舒、PA 和 THMC 通过重塑肠道微生物群和恢复 LDH 后的代谢稳态来缓解炎症和疼痛，从而激活自噬和 Wnt/β-连环蛋白通路，为 LDH 的临床治疗提供了新的治疗靶点。
