Gut microbiome in neuroendocrine and neuroimmune interactions: The case of genistein

The healthy and diverse microbes living in our gut provide numerous benefits to our health. It is increasingly recognized that the gut microbiome affects the host's neurobehavioral state through production of metabolites, modulation of intestinal immunity (e.g., cytokines) and other mechanisms (e.g., gut neuropeptides). By sending the sensed information (e.g., metabolic and immunologic mediators) about the state of the inner organs to the brain via afferent fibers, the vagus nerve maintains one of the connections between the brain and GI tract, and oversees many critical bodily functions (e.g., mood, immune response, digestion and heart rate). The microbiota-gut-brain axis is a bidirectional communication between the gut, its microbiome, and the nervous system. In the present review, the roles of microbiome in neuroendocrine and neuroimmune interactions have been discussed using naturally occurring isoflavones, particularly the phytoestrogen genistein, as there are sex differences in the interactions among the microbiome, hormones, immunity and disease susceptibility. A deep understanding of the mechanisms underlying the interactions among the endocrine modulators, brain, endocrine glands, gut immune cells, vagus nerve, enteric nervous system and gut microbiome will provide important knowledges that may ultimately lead to treatment and prevention of debilitating disorders characterized by deficits of microbiome-neuroendocrine-neuroimmune relationships.