The gut microbiota contribute significantly to the immune system. Low-medium polarity ginsenosides from wild ginseng (LWG) have potential immunomodulatory effects. However, how the LWG regulates gut microbiota to enhance immunity remains unclear. To explore the interaction between gut microbes and metabolites mediating LWG’s immunomodulatory effects, this study examined LWG’s impact on splenocytes and CTX-induced immunosuppressed mice. Metabolomic and metagenomic analyses were conducted in vivo to explore the mechanism by which LWG regulates gut microbiota to enhance immunity. In vitro data suggest that LWG at 4 μg/mL enhances the splenocyte activity. Furthermore, LWG effectively reduces symptoms in immunocompromised mice, including weight loss and intestinal mucosal damage. LWG alleviated gut microbiota disturbance, restored tryptophan metabolites (IA, IAA, and IPA), and significantly increased JNK, ERK, and p38MAPK protein levels, which were downstream of AhR. Our study demonstrated that LWG improves the immunity by reshaping gut microbiota, restoring intestinal mucosa, and boosting the gut microbiota-related metabolism of tryptophan to activate the AhR/MAPK pathway. This research offers new insights into the mechanism by which LWG regulates immune function.

中文翻译：

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来自野山参的中低极性人参皂甙通过肠道微生物群驱动的色氨酸代谢激活 AhR/MAPK 途径来提高免疫力


肠道微生物群对免疫系统有重大贡献。来自野山参的中低极性人参皂甙 （LWG） 具有潜在的免疫调节作用。然而，LWG 如何调节肠道微生物群以增强免疫力仍不清楚。为了探讨肠道微生物与介导 LWG 免疫调节作用的代谢物之间的相互作用，本研究研究了 LWG 对脾细胞和 CTX 诱导的免疫抑制小鼠的影响。在体内进行代谢组学和宏基因组学分析，探讨 LWG 调节肠道菌群以增强免疫力的机制。体外数据表明，4 μg/mL 的 LWG 可增强脾细胞活性。此外，LWG 可有效减轻免疫功能低下小鼠的症状，包括体重减轻和肠道粘膜损伤。LWG 减轻了肠道菌群紊乱，恢复了色氨酸代谢物 （IA、IAA 和 IPA），并显着增加了 AhR 下游的 JNK 、 ERK 和 p38MAPK 蛋白水平。我们的研究表明，LWG 通过重塑肠道菌群、恢复肠粘膜和促进色氨酸的肠道菌群相关代谢以激活 AhR/MAPK 通路来提高免疫力。这项研究为 LWG 调节免疫功能的机制提供了新的见解。