Abstract

The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

MeSH

Cyclic Amp-Dependent Protein Kinases, Protein Kinases, Adenosine Monophosphate, Adenosine, Therapeutics, Gastrointestinal Microbiome, Neurodegenerative Diseases, Microbiota

Cited by

• Therapeutic Potential of Polyphenols in Targeting Th17/Treg Balance for Intestinal Barrier Maintenance. Food Sci Nutr, 2025
• Neurodevelopmental disorders and gut-brain interactions: exploring the therapeutic potential of pycnogenol through microbial-metabolic-neural networks. Front Cell Infect Microbiol, 2025
• The effects of degraded polysaccharides from Acanthopanax senticosus on growth, antioxidant and immune effects in broiler chicks based on intestinal flora. Poult Sci, 2025