Liang Qinghua, Du Hailing, Wang Yajing, Lai Ying, Ren Mengxin, Wei Xiuyan, Xiong Zhili
School of Pharmacy, Shenyang Pharmaceutical University, Benxi 117004, China.
School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
J Pharm Biomed Anal. 2025 Sep 15;263:116942. doi: 10.1016/j.jpba.2025.116942. Epub 2025 May 3.
Postmenopausal osteoporosis (PMOP) was caused by significant deviations in gut microbiota and metabolites. Gushudan (GSD), a small traditional Chinese medicine formula, exerted therapeutic effects including kidney-nourishing and bone-strengthening properties. The therapeutic mechanism of GSD in alleviating kidney-yang deficiency syndrome and secondary osteoporosis was systematically investigated through metabolomics and network pharmacology. However, the mechanisms and impact on gut microbiota through which GSD mitigated PMOP remained to be elucidated. In this study, fecal metabolomics was integrated with gut microbiota analysis to comprehensively investigate modification in intestinal flora and metabolic profiles in PMOP rat models from the gut-bone axis framework. Therefore, the GC-MS-based method integrating non-targeted and targeted metabolomics was established to analyze fecal metabolites. The comprehensive analysis of gut microbial communities was performed using 16S rRNA on fecal samples. In the result, 20 potential biomarkers were successfully identified in the non-targeted metabolomics analysis. Subsequently, 12 metabolites related to amino acid metabolism, energy metabolism and bile acid biosynthesis were quantitatively. Then, ten gut microorganisms with significant changes were discovered through 16S rRNA. Furthermore, alterations in fecal metabolites demonstrated a significant correlation with dysbiosis within the gut microorganisms such as [Ruminococcus]_torques_group, Elusimicrobium, Intestinimonas and Papillibacter. GSD effectively modulated abnormal levels of metabolites such as glycine, lactic acid, succinic acid, cholesterol and deoxycholic acid. Specifically, GSD improved the abundance of [Ruminococcus]_torques_group, Elusimicrobium, Intestinimonas. In conclusion, the gut-bone axis was validated as a novel framework, and gut microbiota modulation was further identified as a promising therapeutic target for the prevention of PMOP.
绝经后骨质疏松症（PMOP）是由肠道微生物群和代谢产物的显著偏差引起的。骨疏丹（GSD）是一种小中药配方，具有补肾壮骨等治疗作用。通过代谢组学和网络药理学系统研究了GSD缓解肾阳虚证和继发性骨质疏松症的治疗机制。然而，GSD减轻PMOP的机制及其对肠道微生物群的影响仍有待阐明。在本研究中，将粪便代谢组学与肠道微生物群分析相结合，从肠-骨轴框架全面研究PMOP大鼠模型中肠道菌群和代谢谱的变化。因此，建立了基于气相色谱-质谱联用（GC-MS）的非靶向和靶向代谢组学相结合的方法来分析粪便代谢产物。使用16S rRNA对粪便样本进行肠道微生物群落的综合分析。结果，在非靶向代谢组学分析中成功鉴定出20种潜在生物标志物。随后，对12种与氨基酸代谢、能量代谢和胆汁酸生物合成相关的代谢产物进行了定量分析。然后，通过16S rRNA发现了10种有显著变化的肠道微生物。此外，粪便代谢产物的变化与肠道微生物群（如扭链瘤胃球菌属、栖粪杆菌属、肠道单胞菌属和乳头杆菌属）的失调显著相关。GSD有效调节了甘氨酸、乳酸、琥珀酸、胆固醇和脱氧胆酸等代谢产物的异常水平。具体而言，GSD提高了扭链瘤胃球菌属、栖粪杆菌属、肠道单胞菌属的丰度。总之，肠-骨轴被确认为一个新的框架，肠道微生物群调节被进一步确定为预防PMOP的一个有前景的治疗靶点。
