# Probiotic Molecules That Inhib Inflammatory Diseases
## 2 Cell Envelope Molecules  
Probiotics' cell envelope molecules have immunomodulatory properties that can reduce pro-inflammatory cytokines, increase production of anti-inflammatory IL-10, generate T regulatory cells (Tregs), and help protect from radiation damage. One of the best characterized anti-inflammatory probiotic molecules is the capsular polysaccharide A (PSA) from _Bacteroides fragilis_. Oral administration of PSA, a zwitterionic polysaccharide, is protective and therapeutic in murine models of colitis and multiple sclerosis by inducing IL-10-secreting Tregs. Protection by PSA is TLR2 and MHCII-dependent, likely due to TLR2 signaling in plasmacytoid dendritic cells to induce Tregs and IL-10 production [15; 16; 17; 18; 64]. Furthermore, _B. fragilis_ produces glycosphingolipids that decrease the number of invariant natural killer T cells in the colonic lamina propria, leading to improved outcomes in a murine colitis model [21; 22]. Recently, _B. fragilis_ PSA was shown to activate colonic DCs and produce IFN-\(\beta\) in a TLR4-dependent manner that enhances resistance to viral infection in murine models [20].  
A polysaccharide peptidoglycan complex on _L. casei_ Shirota was shown to improve ileitis and inhibit IL-6/STAT3 signaling in a murine colitis model using bacterial mutants _in vivo_ and purified peptidoglycan _in vitro_[65]. The oral administration of probiotic _L. rhamnous_ GG mutant with modified lipoteichoic acid (LTA) molecules improved colitis in a murine model, correlating with decreased TLR expression and pro-inflammatory cytokine secretion [53]. Further, oral gavage with WT _L. rhamnous_ GG or intraperitoneal (i.p.) injection with _L. rhamnous_ LTA protected intestinal epithelial cells from radiation injury through the activation of pericryptal macrophages. These macrophages release CXCL12 that binds to CXCR4 on COX-2 expressing mesenchymal stem cells and stimulates the release of PGE, which protects epithelial stem cells from radiation [61]. Supernatants from _L. rhamnous_ GG cultures also reduced eosinophil numbers, goblet cell numbers, and lung inflammation in an allergy inflammation murine model [54]. Peritoneal administration of  
\begin{table}
\begin{tabular}{c c c c} \hline
**Organism** & **Molecule** & **Results** & **Reference** \\ \hline _Lactobacillus sakei_ & LTA & LTA inhibits the secretion of TNF-\(\alpha\) from UVA-exposed & [55] \\  & & & derma fibroblasts. & [56] \\ \hline _Lactobacillus salivarius_ & & & \\ _Ls33_ & & & \\ \hline _Lactobacillus Sp_ & Teichonic acids & Teichonic acid induces IL-10 in a TLR2-dependent manner & [57] \\  & & & in macrophages. & \\ \hline _Lactobacillus_ & & & \\ _paraplantarum BGCG11_ & EPS-\(\alpha\)P & EPS\({}^{\text{LP}}\) reduces pro-inflammatory cytokines in a hyperalgesia & \\  & & & rat model that results in anti-hyperalgesic and & [58] \\  & & & anti-edematous outcomes. & \\ \hline _Lactobacillus plantarum_ & & & \\ _NCII16_ & EPS-\(\alpha\)P & EPS\({}^{\text{LP}}\) regulates the tight junction proteins occluding and & \\  & & & ZO-1 by activating STAT3. & [59] \\ \hline \multirow{6}{*}{_Lactobacillus rhamnous_ & & EPS\({}^{\text{Lr}}\) reduces hydrogen peroxide-induced intestinal & \\  & & & oxidative damage and apoptosis by Keep1/Nrf2 and & \\  & & & & \\ \cline{1-1}  & & & \\ _Lactobacillus rhamnous_ & & & \\ _GG_ & & & \\ \cline{1-1}  & & & \\ \cline{1-1}  & & & \\ \cline{1-1}  & & & \\ \hline \end{tabular}
\end{table}
Table 1: _Cont._isolated peptidoglycan from \(L\). _salivarius_Ls33 protects mice from chemically induced colitis in a NOD2-IL-10-dependent manner [56]. Other cell wall components from probiotics have been identified as listed in Table 1. As suggested above, these examples illustrate the potential for using purified active components of probiotics to treat human diseases prophylactically and therapeutically.