Mechanism of action | Â | Specific probiotic examples |
---|---|---|
Luminal pH modification | Production of lactic acid and acetic acid reduces luminal pH resulting in unfavourable milieu for pathogens | Lactobacillus spp.: pH-dependent reduction in pathogen growth [12] VSL#3: in vivo luminal pH reduction in ulcerative colitis patients [13] |
Bacteriocin production | Bacteriocins are proteins produced by bacteria that inhibit the growth and virulence of other microorganisms. The may be narrow spectrum (inhibit related bacterial strains) or broad spectrum (inhibit a wide range of bacteria, yeasts and moulds) [15] | Mutant Lactobacillus salivarius deficient in bacteriocin gene are unable to protect mice against Listeria monocytogenes infection [14] L. salivarius subspecies produce broad-spectrum bacteriocins [16] |
Disruption of interbacterial communication | Autoinducers are the signalling molecules produced and secreted by bacteria that form the basis of quorum sensing (bacterial communication) | Lactobacillus acidophilus La-5 disrupts quorum sensing and expression of virulence-related genes by Escherichia coli O157:H7 [17] |
Enhanced mucosal barrier function | Increased intestinal epithelial cell mucus production and secretion | Lactobacillus plantarum 299v: increased mucin gene expression in vitro [18] and adherence to colonic cells via a mannose-specific adherence mechanism [74] |
 | Reduced adhesion and invasion of intestinal epithelial cells by enteroinvasive bacteria resulting in reduced translocation | Lactobacillus casei rhamnosus adheres to colonic cells in vitro [75] |
 | Increased production of human β-defensin 2 by epithelial cells | E. coli Nissle 1917: increase in mucin gene expression [76] and production of human β-defensin 2 by colonic cells [77] |
 | Stabilisation of intracellular tight junctions and reduced chloride/water secretion | Streptococcus thermophiles and L. acidophilus reduce water and chloride secretion in response to pathogenic bacteria [78, 79] |
 | Epithelial cell regeneration and reduced apoptosis | Lactobacillus pretreatment of intestinal epithelium reduces disruption of epithelial tight junctions by pathogenic E. coli [80]. Probiotic preparation VSL#3 (see Table 2) prevents redistribution of epithelial tight junction proteins on exposure to pathogenic bacteria [76]. Lactobacillus rhamnosus GG prevents cytokine-mediated apoptosis of intestinal epithelial cells [81]. Lactobacillus casei and Clostridium butyricum both stimulate gut epithelial proliferation in rats [82] |
Colonisation resistance | The probiotic competes with pathogen for nutrients and adhesion in a microbiological niche [5] | L. casei rhamnosus adheres to colonic cells, reduces pathogenic bacterial growth and can persist within the gastrointestinal tract [75, 83] |
 |  | E. coli Nissle 1917 inhibits growth of Shiga-toxin producing E. coli [84] |
Immunological effects | Bacterial-epithelial cross-talk enables luminal probiotic organisms to influence gut-associated lymphoid tissue and innate and adaptive host responses [19, 85]. Toll-like receptors play a central role in mediating this process [86] | VSL#3 has been associated with increased anti-inflammatory and reduced proinflammatory cytokine activity, reduced inducible nitric oxide synthase and matrix metalloproteinase activity in patients with pouchitis [87]. L. plantarum 299v increases IL-10 secretion from macrophages and T cells in patients with ulcerative colitis [88]. L. casei and Lactobacillus bulgaricus significantly reduce TNFα release from inflamed mucosa in Crohn's disease [89]. E. coli Nissle 1917 shows local and systemic anti-inflammatory effects in a murine model of lipopolysaccharide-induced sepsis [90] |
 | Increased promotion of B cells to plasma cells and increased production of immunoglobulins [5] | L. rhamnosus GG: increased circulating IgA, IgG and IgM concentrations in children with gastroenteritis [91, 92]. Pretreatment with probiotic prior to typhoid vaccination leads to increased anti-typhoid antibody titres [93] |
 | Activation and modulation of macrophages, T cells and natural killer cells | L. casei Shirota: cell wall structure potently induces IL-12 production and the probiotic differentially controls the inflammatory cytokine responses of macrophages, T cells and natural killer cells [30, 94, 95]. L. casei Shirota and Bifidobacterium breve administered preoperatively to biliary cancer patients significantly reduce postoperative IL-6, C-reactive protein and white cell count concentrations [30]. L. acidophilus and Bifidobacterium longum increased macrophage phagocytic activity in a murine model [96] |