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Medical Uses  |  Safety

Mechanisms of Action of Probiotics

• Alteration of Immune Response
• Production of Antimicrobial Substance
• Competitive Exclusion
• Other Mechanisms of Action of Probiotics

Alteration of Immune Response

There have been a number of studies, primarily in mice, showing that different probiotics enhance immunological responses as evaluated by various parameters. The major immunological endpoints that have been evaluated include: host defense as it relates to resistance against infection; B-lymphocyte activity including IgM and IgA production; phagocytes as it relates to phagocytic activity among other parameters; T-lymphocytes as measured by natural killer (NK) cell activity; Hematopoiesis as reflected by monocyte to macrophage ratios and macrophage cell levels; and finally allergic reaction measured by IgE production and Th1 or Th2 cell-associated cytokine production.

Perdigon and Alvarez have reviewed the effects of probiotics on the immune state. [1] Isolauri et al. have reviewed the interaction between probiotics and the gastrointestinal immune system. [2]

Some of the major findings are reviewed below. Subcutaneous injections of heat killed L.casei strain shirota to BALB/C, C3H/He, C57BL/6, athymic nu/nu or nu/+ enhanced resistance to systemic C. monocytogenes infection. [3] Swiss albino mice fed live L. Casei were protected against Salmonella typhimuriun infection and secretory IgA in intestinal fluid was elevated. [4]

In vitro studies have demonstrated that heat killed L-plantarum and L-fermentation stimulated the splenocyte B lymphocyte population of C57Bl/6 mice. [6] Mice fed milk fermented with either L. Casei, L. acidophilus, or L. casei plus L. acidophilus had three times the isolated peritoneal macrophage phagocytic activity when compared to mice fed nonfermented milk. [7]

A number of different strains of mice administered L. casei strain Shiroto intravenously had elevated splenic NK cell cytotoxic activity. [8] The multiple observations of enhanced or modulated immune responses elicited by probiotics provides one mechanism by which these microorganisms may confer their health benefits.

Production of Antimicrobial Substance

Most bacterial probiotics produce organic acids, such as acetic and lactic acid, which can act as bacterial growth inhibitors. Some probiotics, for example Lactobacillus, produce hydrogen peroxide when transferred from an anaerobic to aerobic environment. Hydrogen peroxide can inhibit the growth of pathogenic microorganisms. In addition to these general antimicrobials produced by probiotics, there is a long list of other products that have been shown to have antimicrobial activity. L. acidophilus has been shown to produce substances between the molecular weights of 200 and 6,200, some of which are sensitive to proteases and can inhibit staphylococcus, streptococcus, E. coli, and salmonella. [9], [10], [11], [12] Lactobacillus rhamnosum strain GG (LGG) produces a broad spectrum low molecular weight centimicrobial peptide which is plasmid mediated and has activity against staphylococcus, streptococcus, mycobacterium, bacillus, clostridium, Listeria, Bifidobacterium, E. coli, and Salmonella. [13] There have been numerous other probiotics that have been shown to produce antimicrobials including: L. bulgarius, L. reuteri, L. helveticus, L. fermentation, L. plantarum, Lactococcus lactis, and S. cremoris.

The observation that many probiotics produce agents that inhibit bacterial growth or are bacteriocidal can account for the resistance to infection noted with probiotic use.

Competitive Exclusion

Preventing the growth of newly introduced bacterial species can also account for probiotic induced resistance to infection. Animal studies have shown that probiotics can prevent the colonization of gastrointestinal tract by E. coli or Salmonella. Human studies have shown Lactobacillus can prevent adherence of E. coli, Klebsiella, pseudomonas, and aeruginosa to uroepithelial cells. [14]

Other Mechanisms of Action of Probiotics

In addition to the mechanisms of action of probiotics cited above, there have been a number of other mechanisms by which probiotics may express their activity and in some instances there is scientific data to support these citations. Examples of mechanisms of action of probiotics that have been to some extent verified include: alteration of intestinal bacterial metabolic activity, and alteration of the gastrointestinal tract microecology.

The fact that there are underlying explanations for the beneficial health effects that have been noted for probiotics gives additional scientific support for these noted benefits.