Bioactive Compounds from Edible and Medicinal Mushrooms in Obesity–Depression Comorbidity: Gut–Brain Axis Mechanisms and Functional Food Perspectives

Obesity–depression comorbidity involves interconnected metabolic dysfunction, chronic low-grade inflammation, oxidative stress, neuroendocrine dysregulation, gut microbial dysbiosis, and impaired gut–brain communication. Edible and medicinal mushrooms provide nutrients and diverse bioactive compounds, including polysaccharides, terpenoids, nucleosides, sterols, peptides, and phenolic compounds. This narrative review integrates evidence on representative mushroom species, cultivation and fermentation factors affecting their composition, major bioactive compounds and biosynthetic pathways, gut–brain axis-related mechanisms, and opportunities for functional food development. Evidence derived predominantly from in vitro and animal studies suggests that mushroom-derived bioactive compounds may modulate gut microbial composition, intestinal barrier integrity, inflammatory and oxidative pathways, lipid and glucose metabolism, and neuroendocrine signaling. An exploratory database-based analysis further mapped predicted candidate molecular targets associated with inflammatory, metabolic, and neural processes. From a food science perspective, the compositional diversity of mushrooms and their compatibility with cultivation, fermentation, extraction, and formulation provide opportunities for developing conventional foods, functional foods, nutraceuticals, and standardized products. Overall, edible and medicinal mushrooms show promise as food and nutraceutical resources, but their translation into evidence-based functional products requires improved standardization, safety and bioavailability assessments, and well-designed human trials.