Mechanism of Action of Probiotics
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Probiotics ostensibly fulfill their definition through a variety of somewhat disparate, somewhat overlapping mechanisms. These include:
- Regulation of intestinal microbial homeostasis
- Antimicrobial activity
- Pathogen exclusion
Each of the mechanisms may be further subdivided depending on the function involved. For example, with respect to epithelial barrier function, probiotics can conceivably act through general antimicrobial effects, effects on intestinal permeability in the presence of invasive bacteria, effects on epithelial cell inflammatory responses and effects on epithelial cell survival.
Regulation of intestinal microbial homeostasis
In a healty gut, there is an optimum balance among gut flora, the beneficial bacteria, such as Lactobacilli and Bifidobacteria are predominant. Altered equilibrium of microbial community may change luminal immune and inflammatory response as well as metabolism of epithelial cells. Probiotics can regulate intestinal homeostasis by using different mechanisms e.g.
- Reducing adherence and invasion of pathogens because they share different adhesion sites on epithelium with pathogens
- Reinforcing tight junctions and intestinal barrier function by activating various intracellular signalling pathways. These activated proteins induce expression of mucins, antimicrobial peptides (defensins, Cathelicidins) and rearrangement of tight junction proteins
- Probiotics modulate luminal metabolism by production of short chain fatty acids (e.g. Acetate and butyrate). These SCFAs modulate gene expression of epithelial cells by influencing epigenetic modulations. These changes stimulate epithelial proliferation and barrier function.
The antimicrobial attribute of probiotics is related to production of some active metabolites capable of inhibiting or killing potential pathogens as listed below.
- Probiotics ferment sugars and produce organic acids such as lactic acid and acetic acid. The mixtures of organic acids have a powerful antimicrobial activity at low pH.
- Secondary metabolites i.e. ethanol, acetaldehyde, acetoin, carbon dioxide, reuterin, reutericyclin and other germicidal compounds are produced by probiotics. These low molecular weight components works as growth inhibitory or membrane disrupting factors against pathogens.
- Some probiotics strains are able to produce proteinaceous antibiotic like substances designated as bacteriocins. Bacteriocins are ribosomally coded short peptides and exert antimicrobial action by interfering with cell wall synthesis and by causing pore formation in cell wall of the target organisms.
- Hydrogen peroxide is produced by lactic acid bacteria through the action of flavoprotein- containing oxidases, NADH oxidases and superoxide dismutase. Low amount of H2O2 oxidize sulphydryl group of surface proteins and enzymes of target organisms.
Probiotics interact with epithelial cells and dendritic cells (DC) and exert immunomodulatory effect. The effects are strain dependent, induced by profiles of cytokines secreted by lymphocytes or dendritic cells. Interaction of probiotics with these cell’s surface receptors activates some intracellular signalling pathways and induce following immune systems:
- Mucosal immune system – Probiotics induce expression of BAF (B cell activating factor) and APRIL (A proliferating inducing ligand) from epithelial cells and DCs which stimulate secretion of sIgA from luminal B cells.
- Innate and adaptive immune system – Probiotics stimulates production of pro-inflammatory cytokines (TNF-α, IL-8, IL-12, and IFN-γ) from DC cells, but regulates the degree of innate immune activation and prevents excessive inflammation. As well as MAMPs from probiotics expressed by MHC of DC; interact with TCR of T cells and shapes the adaptive immunity of host.
- Th1/Th2 balance - The balance between Th1 and Th2 cytokine production can determine the direction and outcome of an immune response. A deviation towards Th1 is associated with chronic inflammatory diseases whereas an abnormal response of Th2 type characterizes the allergic reactions. It is proposed that consumption of probiotic products could produce an immunomodulatory effect by interfering with helper cell differentiation process through upsetting the Th1/Th2 equilibrium. Different probiotic strains are able to stimulate Pro-inflammatory effect or anti-inflammatory action by alteration of Th1/Th2 ratio toward Th1 or toward Th2 respectively.
A process by which an organism is prevented from colonizing a given environment because of the prior presence of other organisms that are better able to establish and maintain themselves in that environment. Probiotics share the same receptor sites on host cells with pathogens. This property makes them able to exclude pathogens from host intestine, urogenital tract and other host sites. Probiotics excludes intestinal pathogens by following mechanisms:
- Steric hindrance and competitive depletion of essential nutrients
- Competitive exclusion by adhered probiotics, by competition for receptor sites and by displacement of adhered pathogens
- Non competitive exclusion by induction of secretion of antimicrobial components from host cell and by regulation of epithelial barrier function.