Shiitake mushroom as a wholefood supplementation in a Western diet modulates the gut microbiome, serotonergic system, and Wnt-signaling to promote gut health in mice

Authors: GUAN, YINGXUE - University Of Massachusetts; WANG, CHENG - University Of Massachusetts; Zeng, Huawei; MOORE, MATTHEW - University Of Massachusetts; LIU, ZHENHUA - University Of Massachusetts

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/8/2025
Publication Date: 9/23/2025
Citation: Guan, Y., Wang, C., Zeng, H., Moore, M., Liu, Z. 2025. Shiitake mushroom as a wholefood supplementation in a Western diet modulates the gut microbiome, serotonergic system, and Wnt-signaling to promote gut health in mice. Journal of Nutrition. 155(11):3693-3703. https://doi.org/10.1016/j.tjnut.2025.09.021.
DOI: https://doi.org/10.1016/j.tjnut.2025.09.021

Interpretive Summary: Epidemiological studies have shown a linkage between over nutrition, diet-related obesity and increased risk of inflammation and cancer in the colon. A Western-style diet (WD), typically high in fat and low in fiber and certain micronutrients, has been associated to a range of chronic diseases through its impact on gut health. Mushrooms exhibit a distinct nutritional profile that complements the deficiencies commonly associated with WD. We hypothesize that shiitake mushroom as a wholefood supplementation in WD may reduce the risk of obesity-related inflammation and cancer in the colon. In this study, we demonstrated that shiitake mushroom reduced several biochemical markers and bacterial species (in the colon) which were related to colon inflammation and cancer in a mouse model fed with a high-fat diet. These data provide further insights into the health-promoting potential of mushrooms against obesity-related chronic diseases in the colon, and will be useful for scientists who are interested in diet and gut health.

Technical Abstract: A Western-style diet (WD), typically high in fat and low in fiber and certain micronutrients, has been linked to a range of chronic diseases through its impact on gut health. Mushrooms exhibit a distinct nutritional profile that complements the deficiencies commonly associated with WD. This study explored the potential of shiitake mushroom as a wholefood supplementation in WD to improve its quality and gut health. Male C57BL/6 mice (n=12/group) were divided into three dietary groups: low-fat diet (LF, 10% kcal from fat), high-fat diet (HF, 45% kcal from fat), and high-fat diet with 5% shiitake mushroom powder (HFM). Mice were fed these diets for 12 weeks; and feces, blood, and colonic samples were collected at the end of the study for microbiome and molecular analysis. Results showed that HF increased the body weight while the shiitake mushroom supplementation attenuated the effect (p < 0.05). HFM reshaped the gut microbiome, notably with increased abundance of Akkermansia, Lactococcus, and Turicibacter, which are reportedly beneficial to support gut health (p < 0.01). The Shiitake mushroom also altered the gut serotonergic system (p < 0.05), whose implication in gut health merits further research. The HFM group exhibited a reduced Wnt-signaling, as indicated by reduced p-GSK3ß and active ß-catenin, as well as Wnt-signaling downstream genes including Cyclin D1, c-Myc and Axin2, which were otherwise elevated by high-fat diet (p < 0.01). Given the crucial roles of both the gut serotonergic system and the Wnt/ß-catenin pathway in maintaining gut function and health, these findings suggest that incorporating shiitake mushrooms into WD could serve as an effective Food-Is-Medicine strategy to enhance gut health and address related health conditions associated with the industrialized lifestyle.