Probiotics are live microorganisms that provide health benefits to the host when ingested in adequate amounts. The strains most frequently used as probiotics include lactic acid bacteria and bifidobacteria. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects have not been fully elucidated yet. Several important mechanisms underlying the antagonistic effects of probiotics on various microorganisms include the following: modification of the gut microbiota, competitive adherence to the mucosa and epithelium, strengthening of the gut epithelial barrier and modulation of the immune system to convey an advantage to the host. Accumulating evidence demonstrates that probiotics communicate with the host by pattern recognition receptors, such as toll-like receptors and nucleotide-binding oligomerization domain-containing protein-like receptors, which modulate key signaling pathways, such as nuclear factor-ĸB and mitogen-activated protein kinase, to enhance or suppress activation and influence downstream pathways. This recognition is crucial for eliciting measured antimicrobial responses with minimal inflammatory tissue damage. A clear understanding of these mechanisms will allow for appropriate probiotic strain selection for specific applications and may uncover novel probiotic functions. The goal of this systematic review was to explore probiotic modes of action focusing on how gut microbes influence the host.

Keywords:
Antimicrobial responses, Bifidobacteria, Lactic acid bacteria, Lactobacilli, Probiotic mechanism of action, Probiotics
1.
FAO/WHO: Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. 2001. www.fao.org.
2.
Guarner F, Malagelada JR: Gut flora in health and disease. Lancet 2003;361:512–519.
3.
Gourbeyre P, Denery S, Bodinier M: Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions. J Leukoc Biol 2011;89:685–695.
4.
Macpherson AJ, Harris NL: Interactions between comensal intestinal bacteria and the immune system. Nat Rev Immunol 2004;4:478–485.
5.
Frick JS, Schenk K, Quitadamo M, et al: Lactobacillus fermentum attenuates the proinflammatory effect of Yersinia enterocolitica on human epithelial cells. Inflamm Bowel Dis 2007;13:83–90.
6.
McFarland LV: Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006;101:812–822.
7.
Liong MT: Probiotics: Biology, Genetics and Health Aspects. Microbiology Monographs. Heidelberg, Springer, 2011.
8.
Collins JK, Thornton G, Sullivan GO: Selection of probiotic strains for human application. Int Dairy J 1998;8:487–490.
9.
Ouwehand AC, Salminen S, Isolauri E: Probiotics: an overview of beneficial effects. Antonie van Leeuwenhoek 2002;82:279–289.
10.
Collado MC, Gueimonde M, Salminen S: Probiotics in adhesion of pathogens: mechanisms of action; in Watson RR, Preedy VR (eds): Bioactive Foods in Promoting Health, Chennai, Academic Press, Elsevier, 2010, vol 23, pp 353–370.
11.
Yan F, Polk DB: Probiotics and immune health. Curr Opin Gastroenterol 2011;27:496–501.
12.
Lye HS, Kuan CY, Ewe JA, et al: The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens. Int J Mol Sci 2009;10:3755–3775.
13.
Pelletier X, Laure-Boussuge S, Donazzolo Y: Hydrogen excretion upon ingestion of dairy products in lactose-intolerant male subjects: importance of the live flora. Eur J Clin Nutr 2001;55:509–512.
14.
Woodard GA, Encarnacion B, Downey JR, et al: Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: a prospective randomized trial. J Gastrointest Surg 2009;13:1198–1204.
15.
Karska-Wysocki B, Bazo M, Smoragiewicz W: Antibacterial activity of Lactobacillus acidophilus and Lactobacillus casei against methicillin-resistant Staphylococcus aureus (MRSA). Microbiol Res 2010;165:674–686.
16.
Liong MT: Safety of probiotics: translocation and infection. Nutr Rev 2008;66:192–202.
17.
Rafter J, Bennett M, Caderni G, et al: Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr 2007;85:488–496.
18.
Moayyedi P, Ford AC, Talley NJ, et al: The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 2010;59:325–332.
19.
Golowczyc MA, Mobili P, Garrote GL, et al: Protective action of Lactobacillus kefir carrying S-layer protein against Salmonella enterica serovar enteritidis. Int J Food Microbiol 2007;118:264–273.
20.
Williams NT: Probiotics. Am J Health System Pharm 2010;67:449–458.
21.
Ohland CL, Macnaughton WK: Probiotic bacteria and intestinal epithelial barrier function. Am J Physiol Gastrointest Liver Physiol 2010;298:G807–G819.
22.
Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI: Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001;291:881–884.
23.
Hooper LV, Stappenbeck TS, Hong CV, Gordon JI: Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 2003;4:269–273.
24.
Sartor RB: Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 2006;3:390–407.
25.
Anderson RC, Cookson AL, McNabb WC, Park Z, McCann MJ, Kelly WJ, Roy NC: Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation. BMC Microbiol 2010;10:316.
26.
Hummel S, Veltman K, Cichon C, Sonnenborn U, Schmidt MA: Differential targeting of the E-cadherin/β-catenin complex by Gram-positive probiotic lactobacilli improves epithelial barrier function. Appl Environ Microbiol 2012;78:1140–1147.
27.
Zyrek AA, Cichon C, Helms S, Enders C, Sonnenborn U, Schmidt MA: Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKC redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol 2007;9:804–816.
28.
Stetinova V, Smetanova L, Kvetina J, Svoboda Z, Zidek Z, Tlaskalova-Hogenova H: Caco-2 cell monolayer integrity and effect of probiotic Escherichia coli Nissle 1917 components. Neuro Endocrinol Lett 2010;31:51–56.
29.
Parassol N, Freitas M, Thoreux K, Dalmasso G, Bourdet-Sicard R, Rampal P: Lactobacillus casei DN-114001 inhibits the increase in paracellular permeability of enteropathogenic Escherichia coli-infected T84cells. Res Microbiol 2005;156:256–262.
30.
Otte JM, Podolsky DK: Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Am J Physiol Gastrointest Liver Physiol 2004;286:G613–G626.
31.
Dai C, Zhao DH, Jiang M: VSL#3 probiotics regulate the intestinal epithelial barrier in vivo and in vitro via the p38 and ERK signaling pathways. Int J Mol Med 2012;29:202–208.
32.
Bruewer M, Samarin S, Nusrat A: Inflammatory bowel disease and the apical junctional complex. Ann NY Acad Sci 2006;1072:242–252.
33.
Yan F, Polk DB: Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem 2002;277:50959–50965.
34.
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.
35.
Tao Y, Drabik KA, Waypa TS, Musch MW, Alverdy JC, Schneewind O, Chang EB, Petrof EO: Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells. Am J Physiol Cell Physiol 2006;290:C1018–C1030, erratum in 2006;291: C194.
36.
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.
37.
Mattar AF, Teitelbaum DH, Drongowski RA, Yongyi F, Harmon CM, Coran AG: Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model. Pediatr Surg Int 2002;18:586–590.
38.
Kim Y, Kim SH, Whang KY, Kim YJ, Oh S: Inhibition of Escherichia coli O157:H7 attachment by interactions between lactic acid bacteria and intestinal epithelial cells. J Microbiol Biotechnol 2008;18:1278–1285.
39.
Gaudier E, Michel C, Segain JP, Cherbut C, Hoebler C: The VSL# 3 probiotic mixture modifies microflora but does not heal chronic dextran-sodium sulfate-induced colitis or reinforce the mucus barrier in mice. J Nutr 2005;135:2753–2761.
40.
Caballero-Franco C, Keller K, De Simone C, Chadee K: The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 2007;292:G315–G322.
41.
Juntunen M, Kirjavainen PV, Ouwehand AC, Salminen SJ, Isolauri E: Adherence of probiotic bacteria to human intestinal mucus in healthy infants and during rotavirus infection. Clin Diag Lab Immunol 2001;8:293–296.
42.
Beachey EH: Bacterial adherence: adhesin-receptor interactions mediating the attachment of bacteria to mucosal surfaces. J Infect Dis 1981;143:325–345.
43.
Schiffrin EJ, Brassart D, Servin AL, Rochat F, Donnet-Hughes A: Immune modulation of blood leukocytes in humans by lactic acid bacteria: criteria for strain selection. Am J Clin Nutr 1997;66:515S–520S.
44.
Perdigon G, Maldonado Galdeano C, Valdez JC, Medici M: Interaction of lactic acid bacteria with the gut immune system. Eur J Clin Nutr 2002;56:S21–S26.
45.
Hirano J, Yoshida T, Sugiyama T, Koide N, Mori I, Yokochi T: The effect of Lactobacillus rhamnosus on enterohemorrhagic Escherichia coli infection of human intestinal cells in vitro. Microbiol Immunol 2003;47:405–409.
46.
Salminen S, Bouley C, Boutron-Ruault MC, Cummings JH, Franck A, Gibson GR, Isolauri E, Moreau MC, Roberfroid M, Rowland I: Functional food science and gastrointestinal physiology and function. Br J Nutr 1998;80:S147–S171.
47.
Collado MC, Gueimonde M, Hernández M, Sanz Y, Salminen S: Adhesion of selected Bifidobacterium strains to human intestinal mucus and the role of adhesion in enteropathogen exclusion. J Food Prot 2005;68:2672–2678.
48.
Crociani J, Grill JP, Huppert M, Ballongue J: Adhesion of different bifidobacterias strains to human enterocyte-like Caco-2 cells and comparison with in vivo study. Lett Appl Microbiol 1995;21:146–148.
49.
Castagliuolo I, Galeazzi F, Ferrari S, Elli M, Brun P, Cavaggioni A, Tormen D, Sturniolo GC, Morelli L, Palù G: Beneficial effect of auto-aggregating Lactobacillus crispatus on experimentally induced colitis in mice. FEMS Immunol Med Microbiol 2005;43:197–204.
50.
González-Rodríguez I, Sánchez B, Ruiz L, Turroni F, Ventura M, Ruas-Madiedo P, Gueimonde M, Margolles A: Role of extracellular transaldolase from Bifidobacterium bifidum in mucin adhesion and aggregation. Appl Environ Microbiol 2012;78:3992–3998.
51.
Neutra MR, Forstner JF: Gastrointestinal mucus: synthesis, secretion and function; in Johnson LR (ed): Physiology of the Gastrointestinal Tract, ed 2. New York, Raven, 1987.
52.
Ouwehand AC, Salminen S, Tolkko S, Roberts P, Ovaska J, Salminen E: Resected human colonic tissue: new model for characterizing adhesion of lactic acid bacteria. Clin Diag Lab Immunol 2002;9:184–186.
53.
Haller D, Colbus H, Ganzle MG, Scherenbacher P, Bode C, Hammes WP: Metabolic and functional properties of lactic acid bacteria in the gastro-intestinal ecosystem: a comparative in vitro study between bacteria of intestinal and fermented food origin. Syst Appl Microbiol 2001;24:218–226.
54.
Van Tassell ML, Miller MJ: Lactobacillus adhesion to mucus. Nutrients 2011;3:613–636.
55.
Buck BL, Altermann E, Svingerud T, Klaenhammer TR: Functional analysis of putative adhesion factors in Lactobacillus acidophilus NCNCFM. Appl Environ Microbiol 2005;71:8344–8351.
56.
Vélez MP, De Keersmaecker SC, Vanderleyden J: Adherence factors of Lactobacillus in the human gastrointestinal tract. FEMS Microbiol Lett 2007;276:140–148.
57.
Hynönen U, Westerlund-Wikström B, Palva A, Korhonen TK: Identification by flagellum display of an epithelial cell and fibronectin-binding function in the SlpA surface protein of Lactobacillus brevis. J Bacteriol 2002;184:3360–3367.
58.
Goh YJ, Klaenhammer TR: Functional roles of aggregation-promoting-like factor in stress tolerance and adherence of Lactobacillus acidophilus NCFM. Appl Environ Microbiol 2010;76:5005–5012.
59.
Sánchez B, González-Tejedo C, Ruas-Madiedo P, Urdaci MC, Margolles A: Lactobacillus plantarum extracellular chitin-binding protein and its role in the interaction between chitin, Caco-2 cells, and mucin. Appl Environ Microbiol 2011;77:1123–1126.
60.
von Ossowski I, Reunanen J, Satokari R, Vesterlund S, Kankainen M, Huhtinen H, Tynkkynen S, Salminen S, de Vos WM, Palva A: Mucosal adhesion properties of the probiotic Lactobacillus rhamnosus GG SpaCBA and SpaFED pilin subunits. Appl Environ Microbiol 2010;6:2049–2057.
61.
von Ossowski I, Satokari R, Reunanen J, Lebeer S, De Keersmaecker SC, Vanderleyden J, de Vos WM, Palva A: Functional characterization of a mucus-specific LPXTG surface adhesin from probiotic Lactobacillus rhamnosus GG. Appl Environ Microbiol 2011;77:4465–4472.
62.
Candela M, Bergmann S, Vici M, Vitali B, Turroni S, Eikmanns BJ, Hammerschmidt S, Brigidi P: Binding of human plasminogen to Bifidobacterium. J Bacteriol 2007;189:5929–5936.
63.
Candela M, Biagi E, Centanni M, Turroni S, Vici M, Musiani F, Vitali B, Bergmann S, Hammerschmidt S, Brigidi P: Bifidobacterial enolase, a cell surface receptor for human plasminogen involved in the interaction with the host. Microbiology 2009;155:3294–3303.
64.
Candela M, Centanni M, Fiori J, Biagi E, Turroni S, Orrico C, Bergmann S, Hammerschmidt S, Brigidi P: DnaK from Bifidobacterium animalis subsp. lactis is a surface- exposed human plasminogen receptor upregulated in response to bile salts. Microbiology 2010;156:1609–1618.
65.
Guglielmetti S, Tamagnini I, Mora D, Minuzzo M, Scarafoni A, Arioli S, Hellman J, Karp M, Parini C: Implication of an outer surface lipoprotein in adhesion of Bifidobacterium bifidum to Caco-2 cells. Appl Environ Microbiol 2008;74:4695–4702.
66.
Sánchez B, Urdaci MC, Margolles A: Extracellular proteins secreted by probiotic bacteria as mediators of effects that promote mucosa-bacteria interactions. Microbiology 2010;156:3232–3242.
67.
Voltan S, Castagliuolo I, Elli M, Longo S, Brun P, D’Incà R, Porzionato A, Macchi V, Palù G, Sturniolo GC, Morelli L, Martines D: Aggregating phenotype in Lactobacillus crispatus determines intestinal colonization and TLR2 and TLR4 modulation in murine colonic mucosa. Clin Vaccine Immunol 2007;14:1138–1148.
68.
Kim YS, Ho SB: Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep 2010;12:319–330.
69.
Collado MC, Gueimonde M, Sanz Y, Salminen S: Adhesion properties and competitive pathogen exclusion ability of bifidobacteria with acquired acid resistance. J Food Prot 2006;69:1675–1679.
70.
Chauvière G, Coconnier MH, Kerneis S, Fourniat J, Servin AL: Adhesion of human Lactobacillus acidophilus strain LB to human enterocyte-like Caco-2 cells. J Gen Microbiol 1992;138:1689–1696.
71.
Coconnier MH, Klaenhammer TR, Kerneis S, Bernet MF, Servin AL: Protein-mediated adhesion of Lactobacillus acidophilus BG2FO4 on human enterocyte and mucus-secreting cell lines in culture. Appl Environ Microbiol 1992;58:2034–2039.
72.
Greene JD, Klaenhammer TR: Factors involved in adherence of lactobacilli to human Caco-2 cells. Appl Environ Microbiol 1994;60:4487–4494.
73.
Gopal PK, Prasad J, Smart J, Gill HS: In vitro adherence properties of Lactobacillus rhamnosus DR 20 and Bifidobacterium lactis DR 10 strains and their antagonistic activity against an enterotoxigenic Escherichia coli. Int J Food Microbiol 2001;67:207–216.
74.
Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O’neil DA, Macfarlane GT: Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 2005;54:242–249.
75.
Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ: Secretion of microbicidal alphadefensins by intestinal Paneth cells in response to bacteria. Nat Immunol 2000;1:113–118.
76.
O‘neil DA, Porter EM, Elewaut D, Anderson GM, Eckmann L, Ganz T, Kagnoff MF: Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol 1999;163:6718–6724.
77.
Takahashi A, Wada A, Ogushi K, Maeda K, Kawahara T, Mawatari K, Kurazono H, Moss J, Hirayama T, Nakaya Y: Production of beta-defensin-2 by human colonic epithelial cells induced by Salmonella enteritidis flagella filament structural protein. FEBS Lett 2001;508:484–488.
78.
Ogushi K, Wada A, Niidome T, Mori N, Oishi K, Nagatake T, Takahashi A, Asakura H, Makino S, Hojo H, Nakahara Y, Ohsaki M, Hatakeyama T, Aoyagi H, Kurazono H, Moss J, Hirayama T: Salmonella enteritidis FliC (flagella filament protein) induces human betadefensin-2 mRNA production by Caco-2 cells. J Biol Chem 2001;276:30521–30526.
79.
Ganz T: Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003;3:710–720.
80.
Gallo RL, Hooper LV: Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol 2012;12:503–516.
81.
Müller CA, Autenrieth IB, Peschel A: Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci 2005;62:1297–1307.
82.
Koprivnjak T, Peschel A, Gelb MH, Liang NS, Weiss JP: Role of charge properties of bacterial envelope in bactericidal action of human group IIA phospholipase A2 against Staphylococcus aureus. J Biol Chem 2002;277:47636–47644.
83.
Kagan BL, Selsted ME, Ganz T, Lehrer RI: Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proc Natl Acad Sci USA 1990;87:210–214.
84.
Bals R, Wilson JM: Cathelicidins – a family of multifunctional antimicrobial peptides. Cell Mol Life Sci 2003;60:711–720.
85.
Abbot EL, Smith WD, Siou GP, Chiriboga C, Smith RJ, Wilson JA, Hirst BH, Kehoe MA: Pili mediate specific adhesion of Streptococcus pyogenes to human tonsil and skin. Cell Microbiol 2007;9:1822–1833.
86.
Westerlund B, Korhonen TK: Bacterial proteins binding to the mammalian extracellular matrix. Mol Microbiol 1993;9:687–694.
87.
Sun Z, Kong J, Hu S, Kong W, Lu W, Liu W: Characterization of a S-layer protein from Lactobacillus crispatus K313 and the domains responsible for binding to cell wall and adherence to collagen. Appl Microbiol Biotechnol 2012, DOI: 10.1007/s00253-012-4044-x.
88.
Greenberg B: Salmonella suppression by known populations of bacteria in flies. J Bacteriol 1969;99:629–635.
89.
Rolfe RD: Population dynamics of the intestinal tract; in Blankenship LC (ed): Colonization Control of Human Bacterial Enteropathogens in Poultry. San Diego, Academic Press, 1991, pp 59–75.
90.
Servin AL: Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiol Rev 2004;28:405–440.
91.
Chenoll E, Casinos B, Bataller E, Astals P, Echevarría J, Iglesias JR, Balbarie P, Ramón D, Genovés S: Novel probiotic Bifidobacterium bifidum CECT 7366 strain active against the pathogenic bacterium Helicobacter pylori. Appl Environ Microbiol 2011;77:1335–1343.
92.
Sgouras D, Maragkoudakis P, Petraki K, Martinez-Gonzalez B, Eriotou E, Michopoulos S, Kalantzopoulos G, Tsakalidou E, Mentis A: In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota. Appl Environ Microbiol 2004;70:518–526.
93.
Todoriki K, Mukai T, Sato S, Toba T: Inhibition of adhesion of food-borne pathogens to Caco-2 cells by Lactobacillus strains. J Appl Microbiol 2001;91:154–159.
94.
Chu H, Kang S, Ha S, Cho K, Park SM, Han KH, Kang SK, Lee H, Han SH, Yun CH, Choi Y: Lactobacillus acidophilus expressing recombinant K99 adhesive fimbriae has an inhibitory effect on adhesion of enterotoxigenic Escherichia coli. Microbiol Immunol 2005;49:941–948.
95.
Tsai CC, Lin PP, Hsieh YM: Three Lactobacillus strains from healthy infant stool inhibit enterotoxigenic Escherichia coli grown in vitro. Anaerobe 2008;14:61–67.
96.
Muñoz JA, Chenoll E, Casinos B, Bataller E, Ramón D, Genovés S, Montava R, Ribes JM, Buesa J, Fàbrega J, Rivero M: Novel probiotic Bifidobacterium longum subsp. infantis CECT 7210 strain active against rotavirus infections. Appl Environ Microbiol 2011;77:8775–8783.
97.
Nakamura S, Kuda T, An C, Kanno T, Takahashi H, Kimura B: Inhibitory effects of Leuconostoc mesenteroides 1RM3 isolated from narezushi, a fermented fish with rice, on Listeria monocytogenes infection to Caco-2 cells and A/J mice. Anaerobe 2012;18:19–24.
98.
Schiffrin EJ, Blum S: Interactions between the microbiota and the intestinal mucosa. Eur J Clin Nutr 2002;56:S60–S64.
99.
Nesser JR, Granato D, Rouvet M, Servin A, Teneberg S, Karlsson KA: Lactobacillus johnsonii La1 shares carbohydrate-binding specificities with several enteropathogenic bacteria. Glycobiology 2000;10:1193–1199.
100.
Fujiwara S, Hashiba H, Hirota T, Forstner JF: Inhibition of the binding of enterotoxigenic Escherichia coli Pb176 to human intestinal epithelial cell line HCT-8 by an extracellular protein fraction containing BIF of Bifidobacterium longum SBT2928: suggestive evidence of blocking of the binding receptor gangliotetraosylceramide on the cell surface. Int J Food Microbiol 2001;67:97–106.
101.
Mukai T, Asasaka T, Sato E, Mori K, Matsumoto M, Ohori H: Inhibition of binding of Helicobacter pylori to the glycolipid receptors by probiotic Lactobacillus reuteri. FEMS Immunol Med Microbiol 2002;32:105–110.
102.
Coconnier MH, Bernet MF, Chauviere G, Servin AL: Adhering heat-killed human Lactobacillus acidophilus, strain LB, inhibits the process of pathogenicity of diarrhoeagenic bacteria in cultured human intestinal cells. J Diarrhoeal Dis Res 1993;11:235–242.
103.
Tuomola EM, Ouwehand AC, Salminen S: The effect of probiotic bacteria on the adhesion of pathogens to human intestinal mucus. FEMS Immunol Med Microbiol 1999;26:137–142.
104.
Hirn J, Nurmi E, Johansson T, Nuotio L: Long-term experience with competitive exclusion and salmonellas in Finland. Int J Food Microbiol 1992;15:281–285.
105.
Genovese KJ, Anderson RC, Harvey RB, Nisbet DJ: Competitive exclusion treatment reduces the mortality and fecal shedding associated with enterotoxigenic Escherichia coli infection in nursery-raised neonatal pigs. Can J Vet Res 2000;64:204–207.
106.
Alakomi HL, Skytta E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM: Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol 2000;66:2001–2005.
107.
De Keersmaecker SC, Verhoeven TL, Desair J, Marchal K, Vanderleyden J, Nagy I: Strong antimicrobial activity of Lactobacillus rhamnosus GG against Salmonella typhimurium is due to accumulation of lactic acid. FEMS Microbiol Lett 2006;259:89–96.
108.
Makras L, Triantafyllou V, Fayol-Messaoudi D, Adriany T, Zoumpopoulou G, Tsakalidou E, Servin A, DeVuyst L: Kinetic analysis of the antibacterial activity of probiotic lactobacilli towards Salmonella enterica serovar typhimurium reveals a role for lactic acid and other inhibitory compounds. Res Microbiol 2006;157:241–247.
109.
Ouwehand AC: Antimicrobial components from lactic acid bacteria; in Salminen S, von Wright A (eds): Lactic Acid Bacteria: Microbiology and Functional Aspects. New York, Dekker, 1998, pp 139–159.
110.
Russell JB, Diez-Gonzalez F: The effects of fermentation acids on bacterial growth. Adv Microb Physiol 1998;39:205–234.
111.
Nielsen DS, Cho GS, Hanak A, Huch M, Franz CM, Arneborg N: The effect of bacteriocin-producing Lactobacillus plantarum strains on the intracellular pH of sessile and planktonic Listeria monocytogenes single cells. Int J Food Microbiol 2010;141:S53–S59.
112.
Hassan M, Kjos M, Nes IF, Diep DB, Lotfipour F: Natural antimicrobial peptides from bacteria: characteristics and potential applications to fight against antibiotic resistance. J Appl Microbiol. 2012, DOI: 10.1111/j.1365-2672.2012.05338.
113.
Bierbaum G, Sahl: Lantibiotics: mode of action, biosynthesis and bioengineering. Curr Pharm Biotechnol 2009;10:2–18.
114.
O’Shea EF, Cotter PD, Stanton C, Ross RP, Hill C: Production of bioactive substances by intestinal bacteria as a basis for explaining probiotic mechanisms: bacteriocins and conjugated linoleic acid. Int J Food Microbiol 2012;152:189–205.
115.
Yildirim Z, Winters DK, Johnson MG: Purification, amino acid sequence and mode of action of bifidocin B produced by Bifidobacterium bifidum NCFB 1454. J Appl Microbiol 1999;86:45–54.
116.
Liévin V, Peiffer I, Hudault S, Rochat F, Brassart D, Neeser JR, et al: Bifidobacterium strains from resident infant human gastrointestinal microflora exert antimicrobial activity. Gut 2000;47:646–652.
117.
Gibson GR, Wang X: Regulatory effects of bifidobacteria on the growth of other colonic bacteria. J Appl Bacteriol 1994;77:412–420.
118.
Fujiwara S, Hashiba H, Hirota T, Forstner JF: Proteinaceous factor(s) in culture supernatant fluids of bífidobacteria which prevents the binding of enterotoxigenic Escherichia coli to gangliotetraosylceramide. Appl Environ Microbiol 1997;63:506–512.
119.
Fujiwara S, Hashiba H, Hirota T, Forstner JF: Purification and characterization of a novel protein produced by Bifidobacterium longum SBT2928 that inhibits the binding of enterotoxigenic Escherichia coli Pb176 (CFA/II) to gangliotetraosylceramide. J Appl Microbiol 1999;86:615–621.
120.
Macouzet M, Lee BH, Robert N: Production of conjugated linoleic acid by probiotic Lactobacillus acidophilus La-5. J Appl Microbiol 2009;106:1886–1891.
121.
Lee K, Paek K, Lee HY, Park JH, Lee Y: Antiobesity effect of trans-10,cis-12-conjugated linoleic acid-producing Lactobacillus plantarum PL62 on diet-induced obese mice. J Appl Microbiol 2007;103:1140–1146.
122.
Oelschlaeger TA: Mechanisms of probiotic actions – a review. Int J Med Microbiol 2010;300:57–62.
123.
Coloretti F, Carri S, Armaforte E, Chiavari C, Grazia L, Zambonelli C: Antifungal activity of lactobacilli isolated from salami. FEMS Microbiol Lett 2007;271:245–250.
124.
Lindgren SE, Dobrogosz WJ: Antagonistic activities of lactic acid bacteria in food and feed fermentations. FEMS Microbiol Rev 1990;7:149–163.
125.
Prema P, Smila D, Palavesam A, Immanuel G: Production and characterization of an antifungal compound (3-phenyllactic acid) produced by Lactobacillus plantarum strain. Food Bioprocess Technol 2008;3:379–386.
126.
Niku-Paavola ML, Laitila A, Mattila-Sandholm T, Haikara A: New types of antimicrobial compounds produced by Lactobacillus plantarum. J Appl Microbiol 1999;86:29–35.
127.
Sjogren J, Magnusson J, Broberg A, Schnurer J, Kenne L: Antifungal 3-hydroxy fatty acids from Lactobacillus plantarum MiLAB 14. Appl Environ Microbiol 2003;69:7554–7557.
128.
Magnusson J, Schnürer J: Lactobacillus coryniformis subsp. coryniformis strain Si3 produces a broad-spectrum proteinaceous antifungal compound. Appl Environ Microbiol 2001;67:1–5.
129.
Rouse S, Harnett D, Vaughan A, van Sinderen D: Lactic acid bacteria with potential to eliminate fungal spoilage in foods. J Appl Microbiol 2008;104:915–923.
130.
Dal Bello F, Clarke CI, Ryan LAM, Ulmer H, Schober TJ, Ström K, Sjögren J, van Sinderen D, Schnürer J, Arendt EK: Improvement of the quality and shelf life of wheat bread by fermentation with the antifungal strain Lactobacillus plantarum FST 1.7. J Cereal Sci 2007;45:309–318.
131.
Strom K, Sjogren J, Broberg A, Schnurer J: Lactobacillus plantarum MiLAB 393 produces the antifungal cyclic dipeptides cyclo(L-Phe-L-Pro) and cyclo(L-Phe-trans-4-OH-L-Pro) and 3-phenyllactic acid. Appl Environ Microbiol 2002;68:4322–4327.
132.
Gómez-Llorente C, Muñoz S, Gil A: Role of Toll-like receptors in the development of immunotolerance mediated by probiotics. Proc Nutr Soc 2010;69:381–389.
133.
Lebeer S, Vanderleyden J, De Keersmaecker CJ: Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat Rev Microbiol 2010;8:171–184.
134.
Kawai T, Akira S: The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010;11:373–384.
135.
Wells JM: Immunomodulatory mechanisms of lactabacilli. Microb Cell Fact 2011;10(suppl 1):S17.
136.
Vizoso Pinto MG, Rodríguez Gómez M, Seifert S, Waltz B, Holzapfel WH, Franz CM: Lactobacilli stimultates the innate immune response and modulate TLR expression of HT29 intestinal epithelial cells in vitro. Int J Food Microbiol 2009;133:86–93.
137.
Vinderola G, Matar C, Perdigón G: Role of the epithelial cells in the immune effects mediated by Gram-positive probiotic bacteria. Involvement of Toll-like receptors. Clin Diagn Lab Immunol 2005;12:1075–1084.
138.
Shida K, Kiyoshima-Shibata J, Nagaoka M, Nanno M: Peptidoglycan from lactobacilli inhibits interleukin-12 production by macrophages induced by Lactobacillus casei through Toll-like receptor 2-dependent and independent mechanisms. Inmmunology 2009;128:e858–e869.
139.
Abreu MT, Fukata M, Arditi M: TLR signaling in the gut in health and diseases. J Immunol 2005;174:4453–4460.
140.
Castillo NA, Perdigón G, De Moreno de Le Blanc A: Oral administration of a probiotic Lactobacillus modulates cytokine production and TLR expression improving the immune response against Salmonella enteri ca serovar typhimurium infection in mice. BMC Microbiol 2011;11:177–189.
141.
Shimazu T, Villena J, Tohno M, Fujie H, Hosoya S, Shimosato T, Aso H, Suda Y, Kawai Y, Saito T, Makino S, Ikegami S, Itoh H, Kitazawa H: Immunobiotic Lactobacillus jensenii elicits anti-inflammatory activity in porcine intestinal epithelial cells by modulating negative regulators of the Toll-like receptor signaling pathway. Infect Inmmun 2012;80:276–288.
142.
Hoarau C, Lagaraine C, Martin I, Velge-Roussel F, Lecranchu Y: Supernatant of Bifidobacterium breve induces dendritic cell maturation, activation, and survival through a Toll-like receptor pathway. J Allergy Clin Immunol 2006;117:696–702.
143.
Zeuthen LH, Fink LN, Frokiaer H: Toll-like receptor 2 and nucleotide-binding oligomerization domain-2 play divergent roles in the recognition of gut derived lactobacilli and bifidobacteria in dendritic cells. Inmmunology 2008;124:489–502.
144.
Kailova L, Mount Patrick SK, Arganbright KM, Halpern M, Kinouchi T, Dvorak B: Bifidobacterium bifidum reduces apoptosis in the intestinal epithelium in necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2010;299:G1118–G1127.
145.
Liu Y, Fatheree NY, Mangalat N, Rhoads JM: Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-ĸB signaling in the intestine. Am J Physiol Gastrointest Liver Physiol 2012;302:G608–G617.
146.
Weiss DS, Raupach B, Takeda K, Akira S, Zychlinsky A: Toll-like receptors are temporally involved in host defense. J Immunol 2004;172:4463–4469.
147.
Totemeyer S, Foster N, Kaiser P, Maskell DJ, Bryant CE: Toll-like receptor expression in C3H/HeJ and C3H/HeJ mice during Salmonella enterica serovar typhimurium infection. Infect Immun 2003;71:6653–6657.
148.
Giahi L, Aumueller E, Elmadfa I, Haslberger AG: Regulation of TLR4, p38 MAPkinase, IĸB and miRNAs by inactivated strains of lactobacilli in human dendritic cells. Benef Microbes 2012;4:91–98.
149.
Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, et al: Toll-like receptor recognizes bacterial DNA. Nature 2000;408:740–745.
150.
Lee J, Mo JH, Katura K, Alkalay I, Rucker AN, Liu YT, Lee HK, Shen C, Cojocaru G, Shenouda S, et al: Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol 2006;8:1327–1336.
151.
Ghadimi D, de Vrese M, Heller KJ, Schrezenmeir J: Effect of natural commensal-origin DNA on Toll-like receptor 9 (TRL9) signaling cascade, chemokine IL-8 expression, and barrier integrity of polarized intestinal epitelial cells. Inflamm Bowel Dis 2010;16:410–427.
152.
Plantiga TS, van Maren WWC, van Bergenhenegouwen J, Hameetman M, Nierkens S, Jacobs C, de Jong DJ, Joosten LAB, van’t Land B, Garssen J, Adema GJ, Netea MG: Differential Toll-like receptor recognition and induction of cytokine profile by Bifidobacterium breve and Lactobacillus strains of probiotics. Clin Vaccine Immunol 2011;18:621–628.
153.
Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R: TLR4, IL-1R and TNF-R signaling to NF-kappaB: variation on a common theme. Cell Mol Life Sci 2008;65:2964–2978.
154.
Kim CH, Kim HG, Kim JY, Kim NR, Jung BJ, Jeong JH, Chung DK: Probiotic genomic DNA reduces the production of pro-inflammatory cytokine tumor necrosis factor-alpha. FEMS Microbiol Lett 2012;328:13–19.
155.
Hakansson A, Molin G: Gut microbiota and inflammation. Nutrients 2011;3:637–682.
156.
Biswas A, Petnicki-Ocwieja T, Kobayashi KS: Nod2: a key regulator linking microbiota to intestinal mucosal immunity. J Mol Med (Berl) 2012;90:15–24.
157.
Chen G, Shaw MH, Kim YG, Nuñez G: NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol 2009;4:365–398.
158.
Fernandez M, Valenti V, Rockel C, Hermann C, Pot B, Boneca IG, Grangette C: Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut 2011;60:1050–1059.
159.
Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, Fernandes-Alnemeri T, Wu J, Monks BG, Fitzgerald KA, Hornung V, Latz E: Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 2009;183:787–791.
160.
Bauernfeind F, Ablasser A, Bartok E, Kim S, Schmid-Burgk J, Cavlar T, Hornung V: Inflammasomes: current understanding and open questions. Cell Mol Life Sci 2010;68:765–783.
161.
Tohno M, Shimasato T, Aso H, Kitazawa H: Immunobiotic Lactobacillus strains augment NLRP3 expression in newborn and adult porcine gut-associated lymphoid tissues. Vet Immunol Immunopathol 2011;144:410–416.
162.
Hirota SA, Ng J, Lueng A, Khajah M, Parhar K, Li Y, Lam V, Potentier MS, Ng K, Bawa M, McCafferty DM, Rioux KP, Ghosh S, Xaier RJ, Colgan SP, Tschopp J, Muruve D, Macdonald JA, Beck PL: NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. Inflamm Bowel Dis 2011;17:1359–1372.
163.
Anderson JP, Mueller JL, Misaghi A, Anderson S, Sivagnanam M, Kolodner RD, Hoffman HM: Initial description of the human NLRP3 promoter. Gene Immun 2008;9:721–726.
164.
Meylan E, Tschopp J, Karin M: Intracellular pattern recognition receptors in the host response. Nature 2006;442:39–44.
165.
Martinon F, Mayor A, Tschopp J: The inflammasomes: guardians of the body. Annu Rev Immunol 2009;27:229–265.
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2012
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