Jun Kim Ph.D.

It was discussed previously (see here) that short chain fatty acids (SCFAs) produced by the gut microbiota are an important class of molecules that participate in different biochemical pathways in the host. When considering the potential health benefits of probiotics, it is also important to identify molecular interactions to investigate mechanisms behind the suggested benefits. Identification of potentially important molecules is the first step to fully understand and harness the benefits in the most optimal way. This article will discuss one aspect of the molecular interaction: probiotic cell adhesion.

Studies have shown that direct contact between probiotic species and the host cells is required for certain beneficial effects. One such interaction seems to be mediated by lipoteichoic acids (LTAs). Teichoic acids (TAs) are anionic polymers and are a major component of the cell walls of many gram- positive bacteria. In particular, TAs that are attached to the cell membrane are named lipoteichoic acids. LTAs from L. johnsonii La1 and L. acidophilus La 10 inhibited E. coli- and lipopolysaccharide (LPS)-induced interleukin-8 (IL-8) release from epithelial cells [1]. The study suggests that through LTAs, gram-positive bacteria can reduce exaggerated inflammatory responses. Since both LTAs and LPS can bind to CD14, the inhibitory effects of LTAs could be due to competitive binding to CD14 molecules but the underlying mechanism needs further study.

Mucins are a family of glycosylated proteins secreted by epithelial cells. They are known to have a non-immune protective effect from microbial pathogens by creating a physicochemical barrier and interacting with the pathogens. Studies have shown that Lactobacillus plantarum and Lactobacillus rhamnosus adhere to epithelial cells, induce mucin production, and prevented adherence of E. coli strains[2]. Adherence of Lactobacillus strains to epithelial cells was required for induction of mucin expression[3]. How the mucin expression occurs is unclear but the study suggests activation of bacterial receptors on epithelial cells as a potential mechanism.

Other studies show activation of host pathways by direct contact with probiotic cells. L. acidophilus ATCC 4356 activated anti-inflammatory and anti-apoptotic effects in epithelial cells through pathways that involves activation of epidermal growth factor (EGF) receptor, mitogen-activated protein kinases (MAPK), protein-kinase B (Akt), and a reduction in IkB degradation [4–6]. Additionally, L. rhamnosus GG was demonstrated to have anti-apoptotic effects by decreasing proapoptotic molecules such as MAPK p38 when direct contact is established[7]. An unknown cell surface factor in L. reuteri inhibited IkB degradation, demonstrated anti-inflammatory effects, and induced nerve growth factor in epithelial cells[8]. Finally, L. acidopihilus NCFM induced the expression of opioid and cannabinoid receptors in intestinal epithelial cell and had pain relieving effects in the gut[9].

In addition to the discussed observations above, the most important function of adhesion is probably allowing commensal or probiotic cells to adhere to our gut lining and colonize this space. While the mechanism of cell adhesion is more comprehensively documented, the downstream effects of probiotic strain adhesion are less known. Given that gut colonization heavily depends on cell adhesion and adhesion can induce signaling as presented above, cell attachment is likely to mediate many of the important benefits of taking probiotics.

Sources:

1. Vidal K, Donnet-Hughes A, Granato D: Lipoteichoic acids from Lactobacillus johnsonii strain La1 and Lactobacillus acidophilus strain La10 antagonize the responsiveness of human intestinal epithelial HT29 cells to lipopolysaccharide and gram-negative bacteria. Infect Immun 2002, 70:2057–2064.

2. Mack DR, Michail S, Wei S, McDougall L, Hollingsworth MA: Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol 1999, 276:G941–950.

3. Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA: Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut 2003, 52:827–833.

4. Resta-Lenert S, Barrett KE: Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut 2003, 52:988–997.

5. Resta-Lenert S, Barrett KE: Probiotics and commensals reverse TNF-alpha- and IFN-gamma-induced dysfunction in human intestinal epithelial cells. Gastroenterology 2006, 130:731–746.

6. Yan F, Cao H, Cover TL, Whitehead R, Washington MK, Polk DB: Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 2007, 132:562–575.

7. Yan F, Polk DB: Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem 2002, 277:50959–50965.

8. Ma DL, Forsythe P, Bienenstock J: Live Lactobacillus reuteri is essential for the inhibitory effect on tumor necrosis factor alpha-induced interleukin-8 expression. Infection and Immunity 2004, 72:5308–5314.

9. Rousseaux C, Thuru X, Gelot A, Barnich N, Neut C, Dubuquoy L, Dubuquoy C, Merour E, Geboes K, Chamaillard M, et al.: Lactobacillus acidophilus ncfm modulates intestinal pain and induces opioid and cannabinoid receptors in the gut. Gastroenterology 2007, 132:A369-A369.