Intestinal commensal microbes as immune modulators

Abstract

Commensal bacteria are necessary for the development and maintenance of a healthy immune system. Harnessing the ability of microbiota to affect host immunity is considered an important therapeutic strategy for many mucosal and nonmucosal immune-related conditions, such as inflammatory bowel diseases (IBDs), celiac disease, metabolic syndrome, diabetes, and microbial infections. In addition to well-established immunostimulatory effects of the microbiota, the presence of individual mutualistic commensal bacteria with immunomodulatory effects has been described. These organisms are permanent members of the commensal microbiota and affect host immune homeostasis in specific ways. Identification of individual examples of such immunomodulatory commensals and understanding their mechanisms of interaction with the host will be invaluable in designing therapeutic strategies to reverse intestinal dysbiosis and recover immunological homeostasis.

Figure 1. Mutualistic commensals with immunomodulatory effects sustain healthy immune homeostasis

Autobionts are permanent members of the normal commensal microbiota. They control immune homeostasis in the lamina propria by, for example, inducing different subsets of effector T cells (control of T cell homeostasis). The relative proportions of Th17 and Treg cells depend on the relative presence of different autobionts, e.g. in different individuals, different intestinal locations, or at different stages in ontogeny. These mutualistic interactions sustain the healthy steady state. Loss of autobionts and general dysbiosis perturbs also the immune balance of the host. Dysbiosis may occur in multiple ways. Invasive intestinal pathogens cause transient infections, but may lead to longterm perturbations of the microbiota due to strong inflammatory responses against the pathogen. Antibiotic (Abx) treatments or inflammation caused by physical damage to the mucosa may also lead to dysbiosis and the outgrowth of pathobionts, which are permanent members of the microbiota, but do not cause disease in the presence of autobionts. Host genetic factors may also initiate or perpetuate dysbiosis. Dysbiosis leads to loss of the immunomodulatory effects of autobionts and results in a perturbed immune balance, which under appropriate conditions may manifest itself in disease. The disease state augments dysbiosis in a vicious circle. Autobionts and conventional probiotics are both mircoorganisms with beneficial effects. Probiotics have transient effects and can boost host immunity. Autobionts are part of the normal microbiota and have developed evolutionary adaptations to colonize the host, regulate host immunity and establish a healthy immune state. Autobionts can therefore reverse dysbiosis as well as immune homeostasis.