The role of short-chain fatty acids in microbiota–gut–brain communication

Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota–gut–brain crosstalk. However, the pathways through which SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, research directly exploring the role of SCFAs as potential mediators of the effects of microbiota-targeted interventions on affective and cognitive functioning is sparse, especially in humans. This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota–gut–brain interactions. The effects of SCFAs on cellular systems and their interaction with gut–brain signalling pathways including immune, endocrine, neural and humoral routes are described. The effects of microbiota-targeted interventions such as prebiotics, probiotics and diet on psychological functioning and the putative mediating role of SCFA signalling will also be discussed, as well as the relationship between SCFAs and psychobiological processes. Finally, future directions to facilitate direct investigation of the effect of SCFAs on psychological functioning are outlined. Short-chain fatty acids (SCFAs) are speculated to have a key role in microbiota–gut–brain crosstalk, but the pathways influencing psychological functioning have not been fully elucidated. This Review summarizes existing knowledge of how SCFAs might indirectly or directly mediate psychological processes.