Ganoderic Acid A Mitigates Inflammatory Bowel Disease through Modulation of AhR Activity by Microbial Tryptophan Metabolism

• DOI: 10.1021/acs.jafc.4c01166
• Publication Date: 2024-07-30T15:43:30Z
• Authors: Rong-Wei Kou; Zhi-Qing Li; Jia-Lin Wang; Shi-Qi Jiang; Rui-Jing Zhang; Yang-Qing He; Bing Xia; Jin-Ming Gao
• Keywords: Male; Bacteria; Tryptophan; Inflammatory Bowel Diseases; Interleukin-22; Gastrointestinal Microbiome; Mice, Inbred C57BL; Mice; Lanosterol; Disease Models, Animal; Receptors, Aryl Hydrocarbon; Heptanoic Acids; Animals; Humans

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.