(A) A tolerogenic environment is promoted by high-fiber diet and downstream production of SCFAs like acetate and butyrate by the gut microbiome. Acetate and butyrate promote Treg differentiation. Butyrate additionally stimulates regulatory B cells and suppresses pro-inflammatory responses by inhibiting histone deacetylase in macrophages. Beneficial bacteria, such as Bifidobacterium and Alistipes, support immune tolerance by enhancing Treg function, increasing antiinflammatory cytokines (IL-10, TGF-β), and reducing pro-inflammatory cytokines (TNF-α, IL-6). Select probiotics can further induce Tregs. (B) Increased rejection risk is related to heightened inflammatory tone associated with pro-inflammatory microbes such as Desulfovibrio, which increases inflammatory cytokines while suppressing Tregs and antiinflammatory IL-10. Unhealthy dietary habits, such as a high-salt diet, can inhibit protective bacteria, leading to the expansion of pro-inflammatory Th17 cells. High-fat diet is also associated with heightened T cell stimulation and increased rejection risk. Full lines indicate host effects demonstrated in transplant models, with colors signifying protective (green) or detrimental (red) alloimmune effects. Arrows represent stimulatory, and blunt-ended lines inhibitory, relationships. Organ icons refer to the transplanted organ (heart, kidney, skin, or aorta). Dotted lines represent immune effects demonstrated in nontransplant models, of potential relevance for alloimmunity.