# Immunomodulatory Properties of Probiotics and Their Derived Bioactive Compounds
## 6 Challenges and Future Perspectives  
The contribution of probiotics in the maintenance of a healthy gut microbiota and a balanced interaction between commensal bacteria and immune cells is noteworthy. However, a few studies have highlighted impediments in probiotic utilization, despite their accredited beneficial effects on human health. For instance, it has been reported that probiotics administered to eliminate common treatment-related side effects in adult cancer patients led to the development of undesired health issues, including bacteremia, endocarditis, sepsis, and pneumonia [172]. Several factors could account for the initiation of inflammatory responses upon probiotic treatment, such as: significant gut microbiota variability between individuals, probiotic strain-specific function, and bacterial translocation to remote tissues or into the bloodstream [24]. Therefore, it is important to evaluate the  
\begin{table}
\begin{tabular}{c c c} \hline \hline
**Cell Type** & **Immunomodulatory Effect** & **References** \\ \hline \multirow{2}{*}{IECs} & Downregulation of pro-inflammatory cytokines & [133; 136] \\ \cline{2-3}  & Abrogation of IECs activation depending on TLRs and IL-1\(\upbeta\) & [162] \\ \hline \multirow{2}{*}{Neutrophils} & NETs formation & [139; 163] \\ \cline{2-3}  & GPR81 activation, suppression of colonic inflammation & [137; 164] \\ \cline{2-3}  & Cell surface markers modulation and cytokine secretion in & \\ \cline{2-3}  & LPS-activated DCs & [133; 137] \\ \hline \multirow{4}{*}{Macrophages} & GPR81-independent metabolic changes, pro-inflammatory cytokines reduction & [165] \\ \cline{2-3}  & GPR81 activation, suppression of colonic inflammation & [137; 164] \\ \cline{2-3}  & M2 macrophage polarization, IL-10 increase, IL-12 decrease & [166] \\ \cline{2-3}  & Downregulation of cytokine secretion in LPS-activated macrophages & [133] \\ \hline \multirow{2}{*}{Monocytes} & Inhibition of glycolysis, suppression of TNF-\(\alpha\) secretion in the TME & [167] \\ \cline{2-3}  & Glycolysis-dependent inhibition of motility, Th17 differentiation, increased IL-17 levels & [170] \\ \cline{2-3}  & Tregs proliferation & [171] \\ \hline \multirow{2}{*}{CD8+ T cells} & Glycolysis-independent inhibition of motility, loss of cytolytic function & [170] \\ \hline \multirow{4}{*}{IECs: intestinal epithelial cells, TLR: Toll-like receptor, IL-1\(\upbeta\): Interleukin-1\(\upbeta\), NETs: neutrophil extracellular traps, DCs: dendritic cells, GPR81: G-protein-coupled receptor 81, LPS: Lipopolysaccharide, IL-10: Interleukin-10, IL-12: Interleukin-12, TNF-\(\upalpha\): Tumor necrosis factor-\(\alpha\), TME: tumor microenvironment, Th17: T helper 17, IL-17: Interleukin-17, Tregs: Tregulatory cells.} \\ \cline{1-1} \cline{2-3}  & Tregs proliferation & [171] \\ \hline \multirow{4}{*}{CD8+ T cells} & Glycolysis-independent inhibition of motility, loss of cytolytic function & [170] \\ \cline{2-3}  & IECs: intestinal epithelial cells, TLR: Toll-like receptor, IL-1\(\upbeta\): Interleukin-1\(\upbeta\), NETs: neutrophil extracellular traps, DCs: dendritic cells, GPR81: G-protein-coupled receptor 81, LPS: Lipopolysaccharide, IL-10: Interleukin-10, IL-12: Interleukin-12, TNF-\(\upalpha\): Tumor necrosis factor-\(\alpha\), TME: tumor microenvironment, Th17: T helper 17, IL-17: Interleukin-17, Tregs: Tregulatory cells.} \\ \cline{1-1} \cline{2-3}  & IECs: intestinal epithelial cells, TLR: Toll-like receptor, IL-1\(\upbeta\): Interleukin-1\(\upbeta\), NETs: neutrophil extracellular traps, DCs: dendritic cells, GPR81: G-protein-coupled receptor 81, LPS: Lipopolysaccharide, IL-10: Interleukin-10, IL-12: Interleukin-12, TNF-\(\upalpha\): Tumor necrosis factor-\(\alpha\), TME: tumor microenvironment, Th17: T helper 17, IL-17: Interleukin-17, Tregs: Tregulatory cells. risk-benefit ratio prior to probiotic administration to individuals with increased intestinal permeability and immunocompromised patients.