Fig. 5.

A probable cellular mechanism of SCFA-related immune response in gut homeostasis. GPR and TLR work in appropriate correlation. Bacterial PAMP, i.e., toxins, LPS and LTA, stimulated TLR and underlying signalling pathways. They promoted the secretion of pro-inflammatory cytokines, i.e., IL-1β, TNF-α, IL-6, etc. As a result, inflammation is initiated. SCFA, i.e., acetate, propionate, and butyrate, intricately correlate with TLR, i.e., TLR2, TLR3, TLR4, TLR9 and TLR10 via GPR, i.e., GPR41, GPR43, and GPR109A. GPR are inter-connected with SCFA via G proteins, which are heterotrimeric and comprise 3 subunits, alpha (α), beta (β), and gamma (γ). This demonstration explains the stimulation of TLR by PAMP, activation of GPR by SCFA, correlation and trans-membrane signalling activities of GPR and TLR, initiation of pro-inflammatory cytokines-mediated inflammation and other malfunctions, stimulation of anti-inflammatory activity to overcome inflammation, and activation of PPAR, MAPK, NF-κB, and NLRP3 inflammasome pathways and relevant transcription/genes expression in overall immune regulation via SCFA. GPR = G protein-coupled receptors; TLR = toll-like receptors; PAMP = pathogen-associated molecular patterns; LPS = lipopolysaccharide; LTA = lipoteichoic acid; IL-1β = interleukin 1β; TNF-α = tumor necrosis factor α; IL-6 = interleukin 6; SCFA = short chain fatty acids; TLR2 = toll-like receptor 2; TLR3 = toll-like receptor 3; TLR4 = toll-like receptor 4; TLR9 = toll-like receptor 9; TLR10 = toll-like receptor 10; GPR41 = G protein-coupled receptor 41; GPR43 = G protein-coupled receptor 43; GPR109A = G protein-coupled receptor 109 A; PPAR = peroxisome proliferator-activated receptors; MAPK = mitogen activated protein kinase; NF-κB = nuclear factor-kappa B; NLRP3 = NOD (nucleotide-binding oligomerization domain) LRR (leucine-rich repeat) and pyrin domain-containing 3.