Neurochemical Signaling Molecules in Gut–Brain Axis: Microbial Metabolites and Therapeutic Implications

The gut–brain axis is a bidirectional communication network linking the gastrointestinal tract and central nervous system and is significantly influenced by the gut microbiota. Emerging evidence indicates that microbial dysbiosis alters neurodevelopment, neurotransmission, and behavior, contributing to psychiatric and neurodegenerative disorders, such as depression, autism, Parkinson’s disease, and Alzheimer’s disease. Key mediators of this crosstalk are microbial metabolites and neuroactive compounds including γ-aminobutyric acid (GABA), short-chain fatty acids (SCFAs), indole derivatives, and tryptophan metabolites. These bioactive molecules modulate brain function by affecting neuronal signaling, neurotransmitter balance, immune responses, and intestinal barrier integrity. This review emphasizes the chemical and functional roles of these compounds in mediating gut–brain communication. Understanding their structure–activity relationships offer novel insights into therapeutic approaches involving probiotics, prebiotics, dietary modulation, and microbial metabolite targeting. Rather than addressing all disorders, this review focuses on the molecular mechanisms underlying gut-derived neurochemical signaling and its relevance to brain health, highlighting promising strategies for managing neuropsychiatric conditions through microbiota modulation.