低聚木糖通过调控肠道菌群及代谢产物改善代谢功能障碍相关脂肪性肝病的机制研究
Mechanistic Study of Xylo-Oligosaccharides in Improving Metabolic Dysfunction-Associated Steatotic Liver Disease by Modulation of Gut Microbiota and Metabolites
摘要: 目的：代谢功能障碍相关脂肪性肝病(MASLD)是全球常见的慢性肝病之一，临床治疗方案有限。低聚木糖作为一种常见益生元，有研究表明其可通过调节肠道微生态改善肝脏脂质沉积。本研究旨在进一步分析低聚木糖对高脂饮食诱导的MASLD小鼠肠道菌群组成及代谢物谱的影响，并探讨其潜在作用机制。方法：将实验小鼠随机分为高脂饮食组(HFD)和低聚木糖干预组(XOS)，利用高脂饮食建立MASDL模型。检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及甘油三酯(TG)水平；采用H.E染色和油红O染色观察肝脏组织学变化，并依据SAF评分系统评估炎症与纤维化程度。通过16S rRNA测序与代谢组学技术，分别获取两组间的肠道菌群结构与代谢物差异，并推测相关代谢通路。结果：与HFD组相比，XOS组血清ALT、AST及TG水平显著降低(p < 0.05)，肝细胞脂滴沉积明显减少。PCoA与Adonis分析(p < 0.001)提示两组菌群在整体结构与分布上存在显著差异；Wilcoxon分析显示，XOS组中Lactobacillus、Coriobacteriaceae_UCG_002丰度升高，而Prevotellaceae在HFD组中相对较高。代谢组学结果发现，XOS组中有156种代谢物含量上升。多组学相关性分析表明，低聚木糖干预可能通过调节肠道菌群组成，影响甘油磷酸胆碱、鞘氨醇等代谢物水平。结论：低聚木糖可改善高脂饮食诱导的MSALD小鼠肠道菌群结构及代谢产物谱，推测其作用可能与鞘脂代谢、甘油磷酸胆碱代谢等通路调控相关，具体机制尚需进一步研究。
Abstract: Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disorder worldwide, yet effective clinical treatments remain limited. Xylo-oligosaccharides (XOS), a common prebiotic, have been reported to alleviate hepatic lipid accumulation by modulating the gut microbiota. This study aimed to further investigate the effects of XOS on gut microbiota composition and metabolomic profiles in a high-fat diet (HFD)-induced MASLD mouse model, and to explore its potential mechanisms. Methods: Mice were randomly divided into an HFD group and an XOS intervention group. The MASLD model was established via HFD feeding. Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and triglyceride (TG) levels were measured. Histopathological changes in liver tissue were evaluated by hematoxylin-eosin (H&E) and Oil Red O staining, and inflammation and fibrosis were assessed using the SAF scoring system. Gut microbiota composition was analyzed by 16S rRNA sequencing, while metabolomic profiles were obtained via untargeted metabolomics to identify differential metabolites and predict related metabolic pathways. Results: Compared with the HFD group, the XOS group showed significantly reduced serum ALT, AST, and TG levels (p < 0.05), accompanied by markedly decreased hepatic lipid droplet accumulation. Principal coordinates analysis (PCoA) and Adonis testing (p < 0.001) indicated significant differences in overall gut microbiota structure between the two groups. Wilcoxon analysis revealed higher abundances of Lactobacillus and Coriobacteriaceae_UCG_002 in the XOS group, whereas Prevotellaceae was more abundant in the HFD group. Metabolomic profiling identified 156 metabolites with increased levels in the XOS group. Multi-omics correlation analysis suggested that XOS intervention may regulate glycerophosphocholine and sphingolipid-related metabolites by modulating gut microbiota composition. Conclusion: Xylo-oligosaccharides ameliorated gut microbiota dysbiosis and altered metabolite profiles in HFD-induced MASLD mice. The potential mechanism may involve modulation of sphingolipid metabolism, glycerophosphocholine metabolism, and related pathways, although further research is warranted to elucidate the underlying biological processes.
文章引用：韩志伟, 陈力. 低聚木糖通过调控肠道菌群及代谢产物改善代谢功能障碍相关脂肪性肝病的机制研究[J]. 临床医学进展, 2025, 15(10): 2283-2298. https://doi.org/10.12677/acm.2025.15103012

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