Zhang Yulong, Dou Zuman, Li Shanshan, Zhang Huaying, Zeng Shanshui, Zuo Xiangyu, Xiao Yu, Zhang Lingling, Li Zhixin, Zhu Qingfeng, Zhang Wenyang, Niu Hui, Duan Qingfei, Chen Xiaoxia, Li Zhuang, Zhou Hongwei, Wang Qian
Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Ultrason Sonochem. 2025 Jan;112:107200. doi: 10.1016/j.ultsonch.2024.107200. Epub 2024 Dec 13.
Ischemia brain injury is closely associated with the gut microbiota. Polysaccharides, as a typical prebiotic, have been extensively employed in stroke treatment. In our previous study, Pueraria lobata polysaccharide (PLP-3) with antioxidant activity was prepared via water extraction and alcohol precipitation combined with ultrasonic degradation. In this study, the effects of PLP-3 on ischemia brain injury and its regulatory effects on the gut microbiota were further investigated. The results demonstrated that PLP-3 effectively reduced the infarct area, improves neurological function, and alleviates neuronal damage of cerebral ischemia injury. Mechanistically, PLP-3 significantly reduces serum LPS levels in MCAO mice, inhibiting TLR-4 activation in brain tissue and thereby reducing IL-1β and TNF-α levels. Meanwhile, PLP-3 significantly repaired the intestinal barrier injury by increasing the expression of tight junction proteins (ZO-1 and Occludin) and increasing the number of goblet cells. Additionally, the structure and composition of gut microbiota in MCAO mice after PLP-3 intervention, were also significantly changed, especially the enrichment of Lactobacillus and the reduction of Corynebacterium and Staphylococcus. At the same time, short chain fatty acid, metabolites of gut microbiota, were also significantly increased and significantly correlated with the abundance of Lactobacillus. Moreover, LC-MS untargeted metabolomics revealed that PLP-3 significantly improves the intestinal metabolic profile after cerebral ischemia injury, upregulating the amino acid biosynthesis pathway and enriching amino acids such as glutamine and arginine, as well as neuroprotective flavonoids such as fisetin and liquiritigenin. These results suggested that PLP-3 could protect mice from cerebral ischemia-reperfusion injury by regulating gut microbiota and repairing gut barrier, inhibiting brain LPS/TLR4/MyD88 inflammatory pathway, therefore we provide a theoretical basis for PLP-3 as a functional food to prevent ischemic brain injury.
缺血性脑损伤与肠道微生物群密切相关。多糖作为一种典型的益生元，已被广泛应用于中风治疗。在我们之前的研究中，通过水提取、乙醇沉淀结合超声降解制备了具有抗氧化活性的葛根多糖（PLP-3）。在本研究中，进一步研究了PLP-3对缺血性脑损伤的影响及其对肠道微生物群的调节作用。结果表明，PLP-3有效减少梗死面积，改善神经功能，减轻脑缺血损伤的神经元损伤。机制上，PLP-3显著降低MCAO小鼠血清LPS水平，抑制脑组织中TLR-4激活，从而降低IL-1β和TNF-α水平。同时，PLP-3通过增加紧密连接蛋白（ZO-1和闭合蛋白）的表达和增加杯状细胞数量，显著修复肠道屏障损伤。此外，PLP-3干预后MCAO小鼠肠道微生物群的结构和组成也发生了显著变化，尤其是乳酸杆菌的富集以及棒状杆菌和葡萄球菌的减少。同时，肠道微生物群的代谢产物短链脂肪酸也显著增加，且与乳酸杆菌的丰度显著相关。此外，LC-MS非靶向代谢组学显示，PLP-3显著改善脑缺血损伤后的肠道代谢谱，上调氨基酸生物合成途径，富集谷氨酰胺和精氨酸等氨基酸，以及非瑟酮和甘草素等神经保护类黄酮。这些结果表明，PLP-3可通过调节肠道微生物群和修复肠道屏障来保护小鼠免受脑缺血再灌注损伤，抑制脑LPS/TLR4/MyD88炎症通路，因此为PLP-3作为预防缺血性脑损伤的功能性食品提供了理论依据。
