Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria

Abstract

Gastrointestinal (GI) diseases, and in particular those caused by bacterial infections, are a major cause of morbidity and mortality worldwide. Treatment is becoming increasingly difficult due to the increase in number of species that have developed resistance to antibiotics. Probiotic lactic acid bacteria (LAB) have considerable potential as alternatives to antibiotics, both in prophylactic and therapeutic applications. Several studies have documented a reduction, or prevention, of GI diseases by probiotic bacteria. Since the activities of probiotic bacteria are closely linked with conditions in the host's GI-tract (GIT) and changes in the population of enteric microorganisms, a deeper understanding of gut-microbial interactions is required in the selection of the most suitable probiotic. This necessitates a deeper understanding of the molecular capabilities of probiotic bacteria. In this review, we explore how probiotic microorganisms interact with enteric pathogens in the GIT. The significance of probiotic colonization and persistence in the GIT is also addressed.

Keywords: Probiotics; antimicrobial compounds; bacteriocins; colonization; competitive exclusion; enteric pathogens; gastrointestinal tract; lactic acid bacteria.

Figure 1.

Probiotic mechanisms of action against enteric pathogens in the GIT. Probiotics can affect epithelial barrier integrity by numerous mechanisms. These include: A. direct effects on the intestinal epithelial cells (IECs). Probiotics can increase the secretion of mucin glycoproteins by goblet cells that assemble into a thick mucus layer. Probiotics can augment the secretion of antimicrobial proteins (defensins) by IECs that help to eliminate commensals or pathogens that penetrate the mucus layer. Probiotics can enhance the stability of intercellular junctional complexes (tight junctions (TJ)), which decreases the intercellular permeability of IECs to pathogens and other antigens. B. Most probiotics can inhibit enteric pathogens via the production of antimicrobial substances such as bacteriocins. C. Probiotics can compete with commensals and enteric pathogens for adhesion sites in the mucus layer or IECs, thereby preventing harmful colonization and enhancing barrier function. Probiotics can alter the natural gut microbiota composition and/or gene expression, enhancing barrier integrity through the commensal microbiota. Figure created in biorender (http://biorender.io)

Figure 2.

Mucosal immunomodulation by probiotics in the presence of enteric pathogens. A. Down-regulation by probiotic bacteria of pro-inflammatory cytokine (IL-8) secretion in the GIT. Probiotic bacteria (or their products) may dampen an innate immune response by inhibiting the NF-_ƘB inflammatory signaling pathway and influencing the production of IL-8 and subsequent recruitment of inflammatory immune cells to sites of intestinal injury. B. Activation of NF-_ƘB signaling pathway by enteric pathogens, resulting in severe inflammation of intestinal epithelium tissue. C. Probiotic signaling of dendritic cells (DCs) to stimulate the secretion of anti-inflammatory cytokines such as IL-10 in response to an intestinal infection. D. Probiotics can augment the levels of IgA-secreting plasma cells in the lamina propria and promote the transcytosis of secretory IgA (sIgA) across the epithelial cell layer and secretion into the luminal mucus layer, preventing and limiting bacterial penetration of host tissues. IECs, intestinal epithelial cells; IL-8, interleukin 8; IL-10, interleukin 10; MФ, macrophage; NФ, neutrophil; NF-_ƘB, nuclear factor-kappa B. TGFβ, transforming growth factor-β; Th_1-3, T helper cells; T_reg, regulatory T cells. Figure created in biorender (http://biorender.io)