Microbiome, Immunomodulation, and the Neuronal System

Vertebrates harbor both symbiotic and pathogenic bacteria on the body and various mucosal surfaces. Of these surfaces, the intestine has the most diverse composition. This composition is dependent upon various environmental and genetic factors, with diet exerting the maximum influence. Significant roles of the intestinal bacteria are to stimulate the development of a competent mucosal immune system and to maintain tolerance within the intestine. One manner in which this is achieved is by the establishment of epithelial integrity by microbiota found in healthy individuals (healthy microbiota); however, in the case of a disrupted intestinal microbiome (dysbiosis), which can be caused by various conditions, the epithelial integrity is compromised. This decreased epithelial integrity can then lead to luminal products crossing the barrier, generating a systemic proinflammatory response. In addition to epithelial integrity, healthy intestinal commensals metabolize indigestible dietary substrates and produce short-chain fatty acids, which are bacterial metabolites that are essential for colonic health and regulating the function of the intestinal immune system. Intestinal commensals are also capable of producing neuroactive molecules and neurotransmitters that can affect the function of the vagus nerve. The observations that intestinal dysbiosis is associated with different diseases of the nervous system, suggests that cross-talk occurs amongst the gut, the nervous system, and the immune system.