Specificity of the adaptive immune response to the gut microbiota.

The adaptive immune response to normal gut bacteria is part of a homeostatic process that is neither ignorance nor tolerance. Through both targeted and meta-genome sequencing of the gut microbiota, we now know more about the microbial population that inhabits the gut environment than any previous generation. Defining the specificity of the adaptive immune response to gut symbionts and the impact of this specificity on the gut barrier function is still limited by lack of comprehensive data. The evolution of the gut microbiota over millenia with its host provides stability to the present-day microbiota in the presence and absence of the adaptive and innate immune system. Intrinsic factors within each member of the microbiota modulate the immunostimulatory capacity of gut bacteria. Three of these factors, ecological fitness, antigenic degeneracy, and pathogenicity, will control the level of immune response to a given organism in the community. Future research that defines the specificity of microbiota-reactive T and B cells will provide insight into both normal homeostasis as well as the pathology of inflammatory and metabolic diseases associated with the gut microbiome.