Table 5.

Bifidobacteria-influenced metabolites and immunomodulatory properties.

Metabolite	Regulatory Mechanism	Influence	Model/System	References
Butyrate	↑ TGFβ and IL-10 expression (APCs/IECs); ↑ Treg development; colorectal cancer cell apoptosis	Bifidobacterium-produces acetate, which drives Anaerostipes caccae and Eubacterium rectale ATCC 33,656 production of butyrate via butyryl-CoA:acetate CoA-transferase	In vitro and in vivo mouse Treg differentiation; tumor cell line	19,20,108,109
isoDCA (secondary BA)	↓ TNFα and IL-6 in DCs; ↑ Foxp3 induction, peripheral Tregs	Bifidobacterium cannot directly produce isoDCA, but encodes BSH that deconjugates BAs into other secondary BAs which may have similar immunomodulatory roles	In vitro mouse T cell/DC culture; in vivo mouse metabolite treatment	110–112
Spermine	↓ M1 macrophage activation via suppression of ornithine decarboxylase and ↓ pro-inflammatory cytokine synthesis	Bifidobacterium enhances polyamine production from E coli and E. faecalis via luminal acidification	Human PBMCS, mouse macrophage cell lines	33,113,114