Biotransformation of Ganoderma lucidum and Hericium erinaceus for ex vivo gut-brain axis modulation and mood-related outcomes in humans: CREB/BDNF signaling and microbiota-driven synergies

Jan 23, 2025Journal of ethnopharmacology

How processed Ganoderma lucidum and Hericium erinaceus mushrooms may influence the gut-brain connection, mood, brain growth signals, and gut bacteria in humans

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Abstract

Bioactive compounds were confirmed in both Reishi and Lion's Mane mushrooms, including triterpenoids and polysaccharides.

Concentration-dependent changes in metabolic activity and redox balance were observed following treatment with microbiome cell-free supernatants.
Microbiome cell-free supernatants influenced the Nrf2 pathway and activated heat shock proteins, which may provide neuroprotective effects.
Neurotrophic factors such as BDNF, CDNF, and MANF, important for neuronal function, were upregulated in response to treatment.
Alterations in intracellular signaling pathways were noted, particularly in the CREB/BDNF pathway, while some pathways showed no significant changes.
The findings suggest that the interplay between these mushrooms and the gut microbiota could be associated with mood enhancement.

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BACKGROUND: The human gut microbiota plays a crucial role in various aspects of health, extending beyond digestion and nutrient absorption. Ganoderma lucidum (Reishi) and Hericium erinaceus (Lion's Mane), traditional medicinal mushrooms, have garnered interest due to their potential to exert positive health effects. The aim of our study was to investigate the molecular impact of Reishi and Lion's Mane on mood regulation through the gut-brain axis.

METHODS: We utilized a dynamic simulator of the human intestinal microbial ecosystem (SHIME), followed by HPLC-ESI-QTOF-MS/MS and a series of biochemical and molecular assays, including MTT for cell viability, fluorogenic probes for redox balance (ROS and GSH), and Western blot for protein analysis.

RESULTS: Chromatographic analysis confirmed the presence of bioactive compounds in both mushrooms, including triterpenoids (ganoderic acids) and polysaccharides in G. lucidum, as well as hericenones and erinacines in H. erinaceus. We observed concentration-dependent changes in metabolic activity and redox balance due to microbiome cell-free supernatant treatment (M-CFSs). M-CFSs also influenced the Nrf2 pathway and activated heat shock proteins, which may confer neuroprotective effects. Notably, M-CFSs upregulated neurotrophic factors such as BDNF, CDNF, and MANF, crucial for neuronal function. Our study revealed alterations in intracellular signaling cascades, most notably the CREB/BDNF pathway. Moreover, the Akt/mTOR and ERK1/2 showed no significant changes, while Akt/GSK3α/β displayed only partial modifications. The overlapping effects of synaptic activity and activation of the gut-brain axis appear to contribute to mood enhancement.

CONCLUSIONS: These pilot findings suggest a potential role for G. lucidum and H. erinaceus in mood disorder regulation through multifaceted mechanisms involving the gut microbiota. The study underscores the importance of understanding the synergistic interactions between medicinal fungi, gut microbiota, and neural processes to develop novel or preventive strategies for mental health disorders.

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Biotransformation of Ganoderma lucidum and Hericium erinaceus for ex vivo gut-brain axis modulation and mood-related outcomes in humans: CREB/BDNF signaling and microbiota-driven synergies

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