Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is characterized by visceral hypersensitivity and intestinal dysmotility. Ganoderic acid A (GAA), a bioactive triterpenoid from the edible mushroom Ganoderma lucidum, has been reported to exert multiple health-promoting effects; yet, its role in IBS remains unclear. Here, we induced an IBS-like phenotype in C57BL/6 mice by combining the Citrobacter rodentium challenge with water avoidance stress. GAA supplementation markedly alleviated IBS-like symptoms by restoring intestinal motility, regulating enteric nNOS+ and ChAT+ neurons, reducing visceral hypersensitivity, inhibiting colonic inflammation, reinforcing epithelial barrier integrity, and normalizing mast cell activity. Mechanistically, GAA reshaped gut microbiota, changed key tryptophan-metabolizing bacterial taxa, and promoted indole-3-aldehyde (IAld) production, leading to activation of aryl hydrocarbon receptor (AhR) signaling. Additionally, antibiotic treatment abolished the therapeutic benefits of GAA. Collectively, our findings reveal a microbiota-sensing mechanism by which GAA modulates enteric neurons and intestinal homeostasis, providing mechanistic insight and nutritional strategies for managing IBS and related gastrointestinal disorders.
Kou et al. (Wed,) studied this question.