Bifidobacterium is a widely distributed commensal bacterial genus that displays beneficial pro-homeostatic and anti-inflammatory immunomodulatory properties. Depletion or absence ofBifidobacterium 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 variousBifidobacterial species, the likely multifactorial mechanisms underlying these effects remain elusive, in particular, its immune tolerogenic effect. However, recent work has shed light onBifidobacterium surface structural polysaccharide and protein elements, as well as its metabolic products, as commensal mediators of immune homeostasis. This review aims to discuss several mechanismsBifidobacterium 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.

No potential conflict of interest was reported by the authors.

• R01 HL148672/HL/NHLBI NIH HHS/United States
• T32 AI095190/AI/NIAID NIH HHS/United States
• U01 AI170050/AI/NIAID NIH HHS/United States
• UL1 TR003098/TR/NCATS NIH HHS/United States