Short chain fatty acids (SCFA), produced by bacterial fermentation of dietary fibre in the colon, are key mediators in microbiota-gut-brain (MGB) communication. SCFA influence psychological functioning through various pathways, including immune, endocrine, and vagal systems, and may affect brain development, behavior, and mood. SCFA are absorbed in the colon and enter the bloodstream, where they can influence brain function via histone deacetylase (HDAC) inhibition and activation of G-protein coupled receptors (GPRs). SCFA also modulate gut barrier integrity, reduce systemic inflammation, and influence neuroimmune responses. Preclinical studies suggest that SCFA may enhance cognitive function, reduce anxiety, and improve mood by modulating neurotransmitter systems and neurotrophic factors. However, research on the direct effects of SCFA on psychological functioning in humans is limited. SCFA production can be modulated by dietary interventions, probiotics, and prebiotics, which may alter gut microbiota composition and SCFA levels. While some studies suggest that SCFA may benefit neuropsychiatric disorders such as depression, anxiety, and Alzheimer's disease, the mechanisms and clinical relevance remain unclear. Further research is needed to elucidate the role of SCFA in MGB communication and their potential therapeutic applications.Short chain fatty acids (SCFA), produced by bacterial fermentation of dietary fibre in the colon, are key mediators in microbiota-gut-brain (MGB) communication. SCFA influence psychological functioning through various pathways, including immune, endocrine, and vagal systems, and may affect brain development, behavior, and mood. SCFA are absorbed in the colon and enter the bloodstream, where they can influence brain function via histone deacetylase (HDAC) inhibition and activation of G-protein coupled receptors (GPRs). SCFA also modulate gut barrier integrity, reduce systemic inflammation, and influence neuroimmune responses. Preclinical studies suggest that SCFA may enhance cognitive function, reduce anxiety, and improve mood by modulating neurotransmitter systems and neurotrophic factors. However, research on the direct effects of SCFA on psychological functioning in humans is limited. SCFA production can be modulated by dietary interventions, probiotics, and prebiotics, which may alter gut microbiota composition and SCFA levels. While some studies suggest that SCFA may benefit neuropsychiatric disorders such as depression, anxiety, and Alzheimer's disease, the mechanisms and clinical relevance remain unclear. Further research is needed to elucidate the role of SCFA in MGB communication and their potential therapeutic applications.