Associations of microbiome pathophysiology with social activity and behavior are mediated by epigenetic modulations: Avenues for designing innovative therapeutic strategies

A number of investigations have shown that gut microbiome influences humans’ ability to communicate with others, and impairments in social interactions are linked to alterations in gut microbiome composition and diversity, via epigenetic mechanisms. This article reviews the links among gut microbiome, social behavior, and epigenetic shifts relevant to gut microbiome–derived metabolites. First, we discuss how different social determinants of health, such as socioeconomic status, diet, environmental chemicals, migration, ecological conditions, and seasonal changes may influence gut microbiome composition, diversity, and functionality, along with epigenetic alterations and thereby affect social behavior. Next, we consider how gut microbiome–derived metabolites, diet, probiotics, and fecal microbiome transplantation may reduce impairments in social interactions through the adjustment of epigenetic aberrations (e.g., DNA methylation, histone modifications, and microRNAs expression) which may suppress or increase gene expression patterns. Finally, we present the potential benefits and unresolved challenges with the use of gut microbiome-targeted therapeutics in reducing social deficits.