To achieve synchronous regulation of growth and lignocellulose degradation in Pleurotus ostreatus (PO-01) during fungal residue biorefining, we systematically evaluated O₂ gradients (5%, 20%, 40%) and N₂/CO₂ regarding mycelial development, lignocellulose degradation, and bioethanol potential. A total of 20% O₂ emerged as the critical threshold, balancing mycelial growth (which was faster than that under 5% O₂) and lignocellulose degradation (with lignin degradation rate reaching 15.29%). Metabolomics identified 53 aromatic derivatives related to lignin degradation, with their abundance correlating with actual lignin degradation rates. Meanwhile, it clarified the synergistic degradation mechanism and bioinformatics characteristics of key lignin-degrading enzymes and confirmed the AA9 gene associated with cellulose degradation at the molecular level. Measurements of polysaccharide content and ethanol yield revealed that the 20% O₂ environment led to a remarkably high ethanol yield of 101.90 L·ha⁻¹. In contrast, 5% and 40% O₂ concentrations not only reduced the polysaccharide content but also inhibited bioethanol production, highlighting O₂ as a crucial factor in regulating the synergy between growth and degradation. After comprehensive analysis, this study designated 20% O₂ as the optimal parameter for the integrated biorefining of fungal residues, offering a gas-phase solution to overcome industrial bottlenecks in biofuel production.

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.