Defining dysbiosis and its influence on host immunity and disease

Abstract

Mammalian immune system development depends on instruction from resident commensal microorganisms. Diseases associated with abnormal immune responses towards environmental and self antigens have been rapidly increasing over the last 50 years. These diseases include inflammatory bowel disease (IBD), multiple sclerosis (MS), type I diabetes (T1D), allergies and asthma. The observation that people with immune mediated diseases house a different microbial community when compared to healthy individuals suggests that pathogenesis arises from improper training of the immune system by the microbiota. However, with hundreds of different microorganisms on our bodies it is hard to know which of these contribute to health and more importantly how? Microbiologists studying pathogenic organisms have long adhered to Koch's postulates to directly relate a certain disease to a specific microbe, raising the question of whether this might be true of commensal-host relationships as well. Emerging evidence supports that rather than one or two dominant organisms inducing host health, the composition of the entire community of microbial residents influences a balanced immune response. Thus, perturbations to the structure of complex commensal communities (referred to as dysbiosis) can lead to deficient education of the host immune system and subsequent development of immune mediated diseases. Here we will overview the literature that describes the causes of dysbiosis and the mechanisms evolved by the host to prevent these changes to community structure. Building off these studies, we will categorize the different types of dysbiosis and define how collections of microorganisms can influence the host response. This research has broad implications for future therapies that go beyond the introduction of a single organism to induce health. We propose that identifying mechanisms to re-establish a healthy complex microbiota after dysbiosis has occurred, a process we will refer to as rebiosis, will be fundamental to treating complex immune diseases.

Figure 1

A loss of beneficial microbes, expansion of pathobionts, and loss of diversity are events that encompass dysbiosis. During healthy, homeostatic conditions the microbiota is composed of a diversity organisms that are known to benefit host development and health. However, environmental insults, such as antibiotic use or diet can lead to disruptions in the structure of the microbial community. These disruptions can lead to a loss of organisms that are beneficial to the host and a subsequent overgrowth of commensals that have the potential to cause harm, termed pathobionts. Domination of the microbiota by pathobionts can lead to inflammation and pathology. Additionally, multiple studies have described the diversity of contributions made by the various members of the microbiota. Oftentimes, these are non-redundant influences on host health, thus a total loss of diversity in the microbiota can also influence disease progression or severity and thus also represents a dysbiosis event.