Fermentation represents an efficient biotechnological approach to increase the nutritional and functional potential of traditional Chinese medicine. In this study, Lactobacillus plantarum was used to ferment traditional Chinese medicine Astragalus, the differential metabolites in the fermented Astragalus (FA) were identified by ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS), and the ameliorating effect of FA on dextran sulfate sodium (DSS)-induced colitis in mice were further explored. The results showed that 11 differential metabolites such as raffinose, progesterone and uridine were identified in FA, which may help improve the ability of FA to alleviate colitis. Prophylactic FA supplementation effectively improved DAI score, colon length and histopathological lesion in DSS-treated mice. The abnormal activation of the intestinal immune barrier in mice was controlled after FA supplementation, the contents of myeloperoxidase (MPO) and IgE were reduced and the contents of IgA were increased. The intestinal pro-inflammatory factors TNF-α, IL-1β, IL-6, and IL-17 were down-regulated and the anti-inflammatory factors IL-10 and TGF-β were up-regulated, suggesting that FA can intervene in inflammatory status by regulating the balance of Th1/Th2/Th17/Treg related cytokines. In addition, FA supplementation modified the structure of the intestinal microbiota and enriched the abundance of Akkermansia and Alistipes, which were positively associated with the production of short-chain fatty acids. These microbes and their metabolites induced by FA also be involved in maintaining the intestinal mucosal barrier integrity by affecting mucosal immunity. We observed that intestinal tight junction protein and mucous secreting protein ZO-1, occludin, and MUC2 genes expression were more pronounced in mice supplemented with FA compared to unfermented Astragalus, along with modulation of intestinal epithelial cells (IECs) apoptosis, verifying the intestinal mucosal barrier repaired by FA. This study is the first to suggest that FA as a potential modulator can more effectively regulate the inflammatory status and gut microbiota to repair the intestinal barrier damage caused by colitis.

中文翻译：

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发酵黄芪及其代谢物调节炎症状态和肠道微生物群以修复葡聚糖硫酸钠诱导的溃疡性结肠炎的肠屏障损伤

发酵是一种有效的生物技术方法，可以增加传统中药的营养和功能潜力。在这项研究中，植物乳杆菌被用来发酵中药黄芪, 发酵中的差异代谢物黄芪(FA) 通过超高效液相色谱-Q Exactive 混合四极杆-Orbitrap 质谱法 (UPLC-Q-Exactive-MS) 进行鉴定，并进一步研究 FA 对葡聚糖硫酸钠 (DSS) 诱导的小鼠结肠炎的改善作用探索。结果表明，在 FA 中鉴定出棉子糖、孕酮和尿苷等 11 种差异代谢物，这可能有助于提高 FA 缓解结肠炎的能力。预防性补充 FA 可有效改善 DSS 处理小鼠的 DAI 评分、结肠长度和组织病理学损伤。补充FA后小鼠肠道免疫屏障异常激活得到控制，髓过氧化物酶（MPO）和IgE含量降低，IgA含量升高。肠道促炎因子 TNF-α、IL-1β、IL-6、和 IL-17 下调，抗炎因子 IL-10 和 TGF-β 上调，提示 FA 可通过调节 Th1/Th2/Th17/Treg 相关细胞因子的平衡来干预炎症状态。此外，FA 补充剂改变了肠道微生物群的结构并丰富了阿克曼氏菌和阿里斯派斯，这与短链脂肪酸的产生呈正相关。这些由 FA 诱导的微生物及其代谢产物也通过影响粘膜免疫来参与维持肠粘膜屏障的完整性。我们观察到肠道紧密连接蛋白和粘液分泌蛋白 ZO-1、occludin 和 MUC2 基因表达在补充 FA 的小鼠中比未发酵的小鼠更明显黄芪，连同肠上皮细胞 (IEC) 凋亡的调节，验证了 FA 修复的肠粘膜屏障。这项研究首次表明 FA 作为潜在的调节剂可以更有效地调节炎症状态和肠道微生物群，以修复结肠炎引起的肠道屏障损伤。