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Ganoderic Acid A Modulates Enteric Neurons and Intestinal Homeostasis in Irritable Bowel Syndrome by Microbiota
Rong-Wei Kou1, Rui-Jing Zhang2, Bing Xia3
1Department of Applied Chemistry, Xi'an University of Technology, Xi'an 710054, Shaanxi, People's Republic of China.
Journal of Agricultural and Food Chemistry
|January 28, 2026
Summary
Ganoderic acid A (GAA) from Ganoderma lucidum alleviates irritable bowel syndrome (IBS) symptoms by modulating gut bacteria and enteric neurons. This study reveals GAA
Area of Science:
- Gastroenterology and Pharmacology
- Microbiology and Immunology
Background:
- Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder marked by visceral hypersensitivity and dysmotility.
- Ganoderic acid A (GAA), a triterpenoid from Ganoderma lucidum, has known health benefits, but its effect on IBS is unexplored.
Purpose of the Study:
- To investigate the therapeutic potential of Ganoderic acid A (GAA) in a mouse model of irritable bowel syndrome (IBS).
- To elucidate the underlying mechanisms of GAA's action, focusing on gut microbiota, enteric neurons, and intestinal homeostasis.
Main Methods:
- An IBS-like phenotype was induced in C57BL/6 mice using Citrobacter rodentium challenge and water avoidance stress.
- Mice were supplemented with GAA, and outcomes were assessed by measuring IBS symptoms, intestinal motility, neuronal activity, inflammation, barrier integrity, and mast cell activity.
- Gut microbiota composition, tryptophan metabolism, and aryl hydrocarbon receptor (AhR) signaling were analyzed. Antibiotic treatment was used to confirm microbiota dependence.
Main Results:
- GAA supplementation significantly alleviated IBS-like symptoms, improving intestinal motility and reducing visceral hypersensitivity.
- GAA normalized enteric nNOS+ and ChAT+ neurons, reduced colonic inflammation, reinforced epithelial barrier integrity, and normalized mast cell activity.
- GAA modulated the gut microbiota, promoted indole-3-aldehyde (IAld) production via tryptophan-metabolizing bacteria, activating AhR signaling. These benefits were abolished by antibiotic treatment.
Conclusions:
- Ganoderic acid A (GAA) demonstrates significant therapeutic effects against IBS-like symptoms in mice.
- GAA acts through a microbiota-sensing mechanism, influencing gut bacteria, tryptophan metabolism, and AhR signaling to restore intestinal homeostasis.
- These findings highlight GAA as a potential nutritional strategy for managing IBS and related gastrointestinal disorders.
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