# Immunomodulatory Properties of Probiotics and Their Derived Bioactive Compounds
## 5 Probiotic Derived Bioactive Compounds and Immunity
### SCFAs
#### 5.2.2 SCFAs as Immunomodulatory Molecules
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Cell Type** & **Compound** & **Immunomodulatory Effect** & **References** \\ \hline \multirow{8}{*}{IECs} & \multirow{2}{*}{Acetate} & GPR43 and NLRP3 activation, IL-18 production, maintenance of epithelial barrier & [142] \\ \cline{2-3}  & & PPAR-\(\gamma\) activation, \(\beta\)-oxidation and OXPHOS & \\  & & induction, conditions & [1,16,17] \\  & \multirow{2}{*}{Butyrate} & favoring SCFA-producing bacteria & \\ \cline{2-3}  & & NF-kB pathway suppression, anti-inflammatory & \\  & & cytokines increase & [127,144] \\ \cline{2-3}  & \multirow{2}{*}{Acetate, propionate, butyrate} & Restoration of mucosal barrier integrity (5-FU treated & [131] \\  & & Caco-2 and IECs) & \\ \hline \multirow{2}{*}{Neutrophils} & \multirow{2}{*}{Acetate, butyrate} & GPR43 activation, chemotaxis induction, & [3,146] \\  & & p38 MAPK activation & [3,148] \\ \cline{2-3}  & \multirow{2}{*}{Acetate, propionate, butyrate} & Inhibition of ROS and NO production, NF-kB & \\  & & pathway suppression, & [3,148] \\  & & HDAC inhibition & \\ \hline \multirow{2}{*}{Macrophages} & \multirow{2}{*}{Acetate, butyrate} & Pro-inflammatory cytokines reduction, anti-inflammatory & \\  & & cytokine IL-10 increase & [149] \\ \cline{2-3}  & \multirow{2}{*}{Butyrate} & Epigenetic modulations, M2 macrophage polarization, & \\  & & immune tolerance enhancement & [150] \\ \hline \multirow{8}{*}{DCs} & \multirow{8}{*}{Butyrate} & GPR109A activation, Tregs differentiation, IL-18 & \\  & & secretion, protection & [151] \\ \cline{2-3}  & \multirow{2}{*}{Butyrate} & against inflammation–tumorigenesis & \\ \cline{2-3}  & & Balance in Tregs and Th1-Th17 cells population, modulation & \\ \cline{2-3}  & & of gene expression & \\ \cline{2-3}  & \multirow{2}{*}{Acetate, butyrate} & Activation of GPRs, ALDH1a production, & \\  & & increased secretion & [1,3] \\  & & of IgA by plasma cells & \\ \hline NK cells & Butyrate, acetate & NK recruitment, increased IFN-\(\gamma\) production & [140,155] \\ \hline \multirow{3}{*}{CD4+ T cells} & \multirow{2}{*}{Butyrate} & GPR43/GPR41 activation, differentiation to Tregs & \\  & & expressing Foxp3 & \\ \cline{2-3}  & \multirow{2}{*}{Butyrate, acetate} & Th1 activation, mTOR, STAT3 pathways induction, Blimp-1 & \\  & & and IL-10 production & \\ \hline \multirow{3}{*}{CD8+ T cells} & \multirow{2}{*}{Butyrate} & Enhancement of memory CD8+ responses & [158] \\  & & Enhancement of the efficacy of oxaliplatin, amplification of & \\ \cline{2-3}  & \multirow{2}{*}{DCs+ T cell responses} & CD8+ T cell responses & [159] \\ \hline \multirow{3}{*}{B cells} & Acetate, propionate, & OXPHOS- fatty acid synthesis enhancement, differentiation & \\  & & into plasma cells, epigenetic regulation, IL-6 production, & [160,161] \\ \cline{1-1}  & \multirow{2}{*}{Butyrate} & activation of Tfh & \\ \hline \hline \end{tabular} IECs: intestinal epithelial cells, GPR43: G-protein-coupled receptor 43, NLRP93: NOD-like receptor family pyrin domain containing 3, IL-18: Interleukin-18, PPAR-\(\gamma\): peroxisome proliferatorator-activated receptor-\(\gamma\), OXPHOS- oxidative phosphorylation, SCFA: short chain fatty acid, NF-kB: nuclear factor-kB, 5-FU: 5-Fluorouracil, MAPK: mitogen-activated protein kinase, ROS: reactive oxygen species, NO: nitric oxide, HDAC: histone deacetylase, IL-10: Interleukin-10, DCs: dendritic cells, CPR109A: G-protein-coupled receptor 101A, Tregs: T regulatory cells, Th1: T helper 1, Th17: T helper 17, GPRs: G-protein-coupled receptors, ALDH1a: acetaldehyde dehydrogenase class 1A, IgA: immunoglobulin, ANK: Natural killer cells, GPR41: G-protein-coupled receptor 41, Foxp3: forkhead box protein, mTOR: mammalian target of rapamycin, STAT3: signal transducer and activator of transcription 3, Blimp-1: B lymphocyte-induced maturation protein 1, IL-6: Interleukin-6, Thr: T follicular helper cells.  
\end{table} 
Table 2: The effects of probiotic derived SCFAs on immune cells. Lactate also exhibits a great variety of immunomodulatory properties (Table 3).