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.

肠道微生物群的不平衡会引发从肠道扩散到椎间盘的炎症反应，并与腰椎间盘突出症 (LDH)相关。在本研究中，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、代谢稳态和自噬的影响机制。通过穿刺暴露的椎间盘建立LDH大鼠模型。16S rDNA 用于评估肠道微生物组组成。通过 UPLC-MS 分析微生物代谢物。通过粪便微生物移植（FMT）探索PA和THMC在LDH中的作用机制。我们发现药必舒、PA、THMC 和阳性对照药物西乐葆可减轻 LDH 大鼠的椎间盘损伤，并下调 TRPV1、IL-1β 和 IL-18 的表达。此外，腰必舒在 LDH 后降低了颤螺菌目和瘤胃球菌科的丰度。PA 增加了芽孢杆菌的丰度，同时降低了阴性菌和瘤胃球菌科的丰度。代谢组学显示，药必舒增加了 2-己酮、甲基异丁基酮、2-甲基戊-3-酮和十九烷酸的水平，但降低了泛茶氨酸和尿刊酸的水平。PA 和 THMC 降低尿苷和尿刊酸盐水平。Yaobishu、PA 和 THMC 在 LDH 大鼠中激活自噬和 Wnt/β-catenin 通路。此外，抗生素消除了这些影响。FMT-PA 和 FMT-THMC 激活自噬并降低 IL-1β、IL-18、Wnt1、β-catenin 和 TRPV1 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，药必舒、PA和THMC通过重塑肠道菌群和恢复LDH后的代谢稳态来缓解炎症和疼痛，从而激活自噬和Wnt/β-catenin通路，这为LDH的治疗提供了新的靶点。诊所。