The microbiota-gut-brain axis: An emerging role for the epigenome

Through the gut-brain axis, the microorganisms that reside in the gut are able to exert an important influence on the central nervous system. Preclinical and clinical evidence suggests that alterations in the composition of the gut microbiota are involved in gastrointestinal and neurological disorders. During critical neurodevelopmental time periods, such as the early life, changes in gut microbial composition may detrimentally impact neurodevelopment, and subsequently lead to neurological disorders in later life. The finding that neurological disorders persist suggests that epigenetic modifications may be involved in response to disruption of the microbiota-gut-brain axis. Through establishing epigenetic modifications, environmental (microbial) signals can interfere with the cellular gene expression patterns. These long-lasting modifications exert their effects even when the initial stimulus is removed. In this review, we discuss the pathways that provide bidirectional communication between the microbiota and the central and peripheral nervous systems. Furthermore, we summarize how these microorganisms in the gut exert their influence through changing the epigenome in the brain-gut axis. Impact statement Alterations in the composition of gut microbiota may influence the etiology of gastrointestinal and neurological disorders by disturbing the communication in the gut-brain axis. Epigenetic changes in the gut-brain axis may perpetuate these phenotypes even when the gut microbiota has been restored. The studies reviewed in this article provide an overview of the influence the microbiota exerts onto its host's epigenome. First, we summarize the bidirectional pathways through which the microbiota and the gut-brain axis communicate. Second, we provide evidence for the epigenome-altering capacity of the gut microbiota. Finally, we address the existing knowledge gaps and highlight the potential role of the epigenome in the microbiota-gut-brain axis.