Fig. 3.

Schematic presentation of gut eubiosis and homeostasis. Intact gut epithelium maintains eubiosis and homeostatic balance. Most of the pathogens remained in the gut lumen, whereas the commensal bacteria elicited the underlying mechanisms via producing SCFA and triggering innate and adaptive immune regulation. SCFA via their GPR and (correlated) TLR modulate the immune regulation. During innate immune regulation (the left grey colour representation in the figure), SCFA, especially butyrate, induced apoptosis via activating the neutrophils and macrophages. On the other hand, activation of natural killer and dendritic cells, differentiation of macrophages and dendritic cells, and recruitment of neutrophils and macrophages were reduced. Th1-mediated cytokine productions from macrophages and dendritic cells, and neutrophilic induced cytotoxic effects and cytokine secretion were also reduced. During adaptive immune regulation (the right grey colour representation in the figure), SCFA, via GPR/TLR receptors activated B cells, Naïve T cells, and T regulatory cells (Treg). Treg were either directly activated by propionate or were indirectly activated by butyrate via Naïve T cells. B cells produced IgA, which inhibits bacterial invasion through the gut epithelium. Treg suppressed inflammatory and allergic responses, and its differentiation ameliorated colitis. Additionally, butyrate via HDAC modulated proliferation and recruitment of T cells (Th1, Th2, Th17), induced apoptosis, thus regulated cytokine production. SCFA properly maintain the gut eubiosis and homeostasis via both innate and adaptive immune regulation. SCFA = short chain fatty acids; GPR = G protein-coupled receptors; TLR = Toll-like receptors; Th1 = T helper type 1 cells; Th2 = T helper type 2 cells; Th17 = T helper type 17 cells; Treg = T regulatory cells; IgA = immunoglobulin A; HDAC = histone deacetylases.