Abstract：
Inflammatory bowel disease (IBD), including Crohn\'s disease and ulcerative colitis, is a complex gastrointestinal condition influenced by genetic, microbial, and environmental factors, among which the gut microbiota plays a crucial role and has emerged as a potential therapeutic target. Ganoderic acid A (GAA), which is a lanostane triterpenoid compound derived from edible mushroom Ganoderma lucidum, has demonstrated the ability to modulate gut dysbiosis. Thus, we investigated the impact of GAA on IBD using a dextran sodium sulfate (DSS)-induced colitis mouse model. GAA effectively prevented colitis, preserved epithelial and mucus layer integrity, and modulated the gut microbiota. In addition, GAA promoted tryptophan metabolism, especially 3-IAld generation, activated the aryl hydrocarbon receptor (AhR), and induced IL-22 production. Fecal microbiota transplantation validated the mediating role of the gut microbiota in the IBD protection conferred by GAA. Our study suggests that GAA holds potential as a nutritional intervention for ameliorating IBD by influencing the gut microbiota, thereby regulating tryptophan metabolism, enhancing AhR activity, and ultimately improving gut barrier function.
摘要：
炎症性肠病(IBD),包括克罗恩病和溃疡性结肠炎，是一种受遗传影响的复杂胃肠道疾病，微生物，和环境因素，其中肠道微生物群起着至关重要的作用，并已成为潜在的治疗靶点。灵芝酸A(GAA),这是一种来自食用蘑菇灵芝的羊毛甾烷三萜类化合物，已经证明了调节肠道生态失调的能力。因此，我们使用葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型研究了GAA对IBD的影响。GAA有效预防结肠炎，保存的上皮和粘液层的完整性，并调节肠道微生物群。此外,GAA促进色氨酸代谢，特别是3-IAld一代，激活芳烃受体（AhR），并诱导IL-22的产生。粪便微生物群移植验证了肠道微生物群在GAA赋予的IBD保护中的介导作用。我们的研究表明，GAA具有作为通过影响肠道微生物群改善IBD的营养干预的潜力，从而调节色氨酸代谢，增强AhR活性，并最终改善肠道屏障功能。
