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.

Background: 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 a WD.

Objective: This study explored the potential of shiitake mushrooms as a wholefood supplement in WD to improve its quality and gut health.

Methods: Male C57BL/6 mice (n=12/group) were divided into three dietary groups for 12 weeks: 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). Feces, blood, and colonic samples were collected at the end of the study for microbiome and molecular analysis.

Results: Results showed that the HF increased the body weight while the shiitake mushroom supplementation attenuated the effect (p < 0.05). The 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 reduced Wnt-signaling, as indicated by reduced active β-catenin, as well as downstream genes including Cyclin D1, c-Myc and Axin2, which were otherwise elevated by high-fat diet (p < 0.01).

Conclusions: Given the crucial roles of both the gut serotonergic system and the Wnt/β-catenin pathway in maintaining gut function and health, these findings suggest that incorporating shiitake mushrooms into WD could serve as a promising Food-Is-Medicine strategy to enhance gut health and address related health conditions associated with the industrialized lifestyle.