The other genome: Pathways for the Effects of the Microbiome on Metabolism, Behavior, and mental Disorders

Abstract

Overall Abstract Major efforts are ongoing to unravel the genomic basis of psychiatric disorders, with a focus on the human genome. The amount of microbial cells exceeds that of human cells in our bodies. The immense amount of non-human DNA within our bodies is not captured by traditional human genomic studies. Our microbial component is represented by approximately 1,000 different species. This symposium will address the behavioral effects of our “other genome”: the human microbiome. The microbiota–gut–brain (MGB) axis is a complex multiorgan bidirectional signaling system between the microbiota and the brain that plays a fundamental role in host physiology, homeostasis, development, metabolism and behavior. Growing evidence shows reproducible and consistent effects of microbial states on behavior, supporting a role for the microbiota in modulating behavior. Differences in anxiety-related behaviors are commonly reported in mice with altered gut microbiomes, implicating the role of gut microbiota in stress and depression. In this symposium, Dr. Omry Koren, Bar-Ilan University, Israel, will present data on how microbes can influence mood and behavior. Dr. Peng Xie, Chongqing Medical University, China, will present exciting new data showing that the absence of gut microbiota in germ-free mice results in decreased depressive-like behavior. His team shows that from clinical sampling, the gut microbiotic compositions of healthy controls are significantly different from those of depressed patients. Finally, fecal microbiota transplantation of germ-free mice with ‘depression microbiota’ from depressed patients results in depression-like behaviors compared with colonization with ‘healthy microbiota’ from healthy individuals. Moreover, they showed that mice harboring ‘depression microbiota’ primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism, indicating that the development of depressive-like behaviors is mediated through the host’s metabolism. Dr. Julio Licinio, South Australian Health & Medical Research Institute (SAHMRI) and Flinders University, Australia, will show data on how a model of chronic stress, resulting in depressive-like behaviors, causes change in gut microbiota composition. Dr. Ma-Li Wong, SAHMRI and Flinders, Australia, will present data demonstrating that that the inflammasome, as evidenced by genetic or pharmacologic inhibition of caspase 1, mediates behavioral changes that might be brought about through the MGB axis. In this symposium we will demonstrate that MGB axis is fully bidirectional, functioning in a manner through which variation in microbiota affect behavior, while alterations in behavior, brought about by chronic stress, genetic manipulation or pharmacological intervention, result in changes in the gut microbiota. Further elucidation of the MGB axis may offer novel therapeutic targets for psychiatric disorders.