Bifidobacterium mechanisms of immune modulation and tolerance

Bifidobacterium is a widely distributed commensal bacterial genus that displays beneficial pro-homeostatic and anti-inflammatory immunomodulatory properties. Depletion or absence of Bifidobacterium in humans and model organisms is associated with autoimmune responses and impaired immune homeostasis. At the cellular level, Bifidobacterium upregulates suppressive regulatory T cells, maintains intestinal barrier function, modulates dendritic cell and macrophage activity, and dampens intestinal Th2 and Th17 programs. While there has been a large volume of literature characterizing the probiotic properties of various Bifidobacterial species, the likely multifactorial mechanisms underlying these effects remain elusive, in particular, its immune tolerogenic effect. However, recent work has shed light on Bifidobacterium surface structural polysaccharide and protein elements, as well as its metabolic products, as commensal mediators of immune homeostasis. This review aims to discuss several mechanisms Bifidobacterium utilizes for immune modulation as well as their indirect impact on the regulation of gut microbiome structure and function, from structural molecules to produced metabolites. These mechanisms are pertinent to an increasingly networked understanding of immune tolerance and homeostasis in health and disease.