(P12-009-25) The Effects of Incorporating Shiitake Mushrooms Into a High-Fat Diet on the Gut Microbiome, Serotonin Pathway, and Wnt-Signaling in Mice

Objectives: A Western-style diet, typically low in fiber and micronutrients but high in fat, has been implicated in tumorigenesis. As mushrooms are generally rich in many vitamins, minerals and fiber, this study examines the potential protective effects of shiitake mushroom on gut microbiota and metabolic pathways in the context of a high-fat diet.

Methods: Male C57BL/6 mice (n=12 per 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 supplementation (HFM). Mice were fed these diets for 12 weeks, with food intake and body weight monitored weekly. At the end of the study, blood, intestinal epithelium and fecal contents were collected for molecular and microbiome analysis.

Results: Compared to the LF, the HF and HFM diets significantly altered gut microbial beta diversity, with a dramatic increase in the abundance of beneficial genera such as Faecalibaculum associated with mushroom supplementation (p < 0.001). Shiitake mushroom supplementation was linked to a reduced serotonin (5-HT) release (3.8%) but increased expressions of several serotonin receptors (p < 0.05). Furthermore, in the HFM group, the two critical components within the tumorigenic Wnt pathway, p-GSK3β and active β-catenin, were significant reduced. This was accompanied by an upregulation of Wnt-signaling upstream antagonists, SFRP4, SFRP5, and DKK1, and a downregulation of downstream targets including Cyclin D1, C-myc and Axin 2 (p < 0.05), collectively indicating a suppression of the Wnt-signaling.

Conclusions: These findings indicate that the incorporation of shiitake mushroom into a high-fat diet has the potential to reshape the gut microbiome, modulate serotonin pathways, and inhibit Wnt/β-catenin signaling, offering possible tumorigenic protective effects in a diet-induced obese status.

Funding Sources: This material is based upon work supported in part by a USDA/NIFA AFRI grant (2022-67018-36986, ZL), a USDA-ARS Research Project (3062-10700-002-000D, HZ) and a USDA//NIFA Hatch project (MAS00586, ZL). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the USDA or NIFA.