PROBIOTIC-HUMAN IMMUNE SYSTEM INTERACTIONS

Abstract

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. These microorganisms are known to provide beneficial health effects by competing with pathogens, providing epithelial cell stability and showing regulatory effects on the immune system. They provide immunomodulatory, anti-inflammatory, anti-microbial, antioxidant effects with their released metabolites, produced molecules and cell structure components. Effector molecules of probiotics such as peptidoglycan, teichoic acid, lipoteichoic acid, cell surface polysaccharides, secreted proteins and surface proteins are recognized by innate immunity receptors and activate the immune system. The mechanisms of some effector molecules of probiotics have been elucidated. The aim of this review is to give information on the effects of probiotics and their active molecules known to be used for probiotic-host interactions.

Keywords

• Probiotics,Health Effects,Probiotic-host interactions,Immunomodulation,Effector molecules

PROBİYOTİK- İNSAN BAĞIŞIKLIK SİSTEMİ ETKİLEŞİMLERİ

Öz

Probiyotikler yeterli miktarda tüketildiklerinde sağlık üzerine yararlı etkiler gösteren canlı mikroorganizmalardır. Bu mikroorganizmalar, patojenlerle mücadele, epitel hücre kararlılığını sağlama ve bağışıklık sistemini düzenleyebilmeleri ile sağlık üzerine olumlu etkiler göstermektedirler. Bağışıklık düzenleyici, anti-inflamatuar, anti-mikrobiyal, anti-oksidan etkilerini, açığa çıkardıkları metabolitleriyle, ürettikleri moleküllerle ve hücre yapı bileşenleriyle sağlamaktadırlar. Peptidoglikan, teikoik asit, lipoteikoik asit, hücre yüzey polisakkaritleri, salgılanan proteinler ve yüzey proteinleri gibi probiyotik etken molekülleri doğal bağışıklıkta görevli reseptörler tarafından tanınarak bağışıklık sistemini harekete geçirmektedir. Yapılan çalışmalarla bu etken moleküllerinden bazılarının etki mekanizmaları aydınlatılmıştır.Bu derlemede probiyotiklerin, probiyotik-konak etkileşimleri için kullandıkları bilinen etken molekülleri hakkında ve etkileri üzerine bilgi verilmesi amaçlanmıştır.

Anahtar Kelimeler

• Probiyotikler,Sağlık etkileri,Probiyotik-konak etkileşimleri,Bağışıklık düzenleme,Etken moleküller

References

1. Agrawal, R. (2005). Probiotics: An emerging food supplement with health benefits. Food Biotechnology, 19(3), 227-246. https://doi.org/10.1080/08905430500316474
2. Aguilar-Toalá, J.E., Garcia-Varela, R., Garcia, H.S., Mata-Haro, V., González-Córdova, A.F., Vallejo-Cordoba, B., Hernández-Mendoza, A. (2018). Postbiotics: An evolving term within the functional foods field. Trends in Food Science & Technology, 75, 105-114. https://doi.org/10.1016/j.tifs.2018.03.009
3. Akira, S., Uematsu, S., Takeuchi, O. (2006). Pathogen recognition and innate immunity. Cell, 124(4), 783-801. https://doi.org/10.1016/j.cell.2006.02.015
4. Al-Hassi, H.O., Mann, E.R., Sanchez, B., English, N.R., Peake, S.T.C., Landy, J., Man, R., Urdaci, M., Hart, A. L., Fernandez-Salazar, L., Lee, G.H., Garrote, J.A., Arranz, E., Margolles, A., Stagg, A.J., Knight, S.C., Bernardo, D. (2014). Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp. Molecular Nutrition and Food Research, 58(5), 1132-1143. https://doi.org/10.1002/mnfr.201300596
5. Bäuerl, C., Pérez-Martínez, G., Yan, F., Polk, D.B., Monedero, V. (2010). Functional analysis of the p40 and p75 proteins from lactobacillus casei BL23. Journal of Molecular Microbiology and Biotechnology, 19, 231-241. https://doi.org/10.1159/000322233
6. Bernardo, D., Sánchez, B., Al-Hassi, H.O., Mann, E.R., Urdaci, M.C., Knight, S.C., Margolles, A. (2012). Microbiota/host crosstalk biomarkers: Regulatory response of human intestinal dendritic cells exposed to Lactobacillus extracellular encrypted peptide. PLoS ONE, 7(5), 1-8. https://doi.org/10.1371/journal.pone.0036262
7. Boirivant, M., Strober, W. (2007). The mechanism of action of probiotics. Current Opinion in Gastroenterology, 23(6), 679-692. https://doi.org/10.1097/MOG.0b013e3282f0cffc
8. Bron, P.A., Tomita, S., van Swam, I.I., Remus, D.M., Meijerink, M., Wels, M., Okada, S., Wells, J.M., Kleerebezem, M. (2012a). Lactobacillus plantarum possesses the capability for wall teichoic acid backbone alditol switching. Microbial Cell Factories, 11(123), 1-15. https://doi.org/10.1186/1475-2859-11-123

9. Bron, P. A., Van Baarlen, P., Kleerebezem, M. (2012b). Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nature Reviews Microbiology, 10, 66-78. https://doi.org/10.1038/nrmicro2690
10. Chapot-Chartier, M.P., Kulakauskas, S. (2014). Cell wall structure and function in lactic acid bacteria. Microbial Cell Factories, 13(1), 1-23. https://doi.org/10.1186/1475-2859-13-S1-S9
11. Ciszek-Lenda, M., Nowak, B., Śróttek, M., Gamian, A., Marcinkiewicz, J. (2011). Immunoregulatory potential of exopolysaccharide from Lactobacillus rhamnosus KL37. Effects on the production of inflammatory mediators by mouse macrophages. International Journal of Experimental Pathology, 92(6), 382-391. https://doi.org/10.1111/j.1365-2613.2011.00788.x
12. Claes, I.J.J., Segers, M.E., Verhoeven, T.L.A., Dusselier, M., Sels, B.F., De Keersmaecker, S.C.J., Sigrid, C.J., Vanderleyden, J., Lebeer, S. (2012). Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG. Microbial Cell Factories, 11(161), 1-8. https://doi.org/10.1186/1475-2859-11-161
13. Claes, I.J.J., Lebeer, S., Shen, C., Verhoeven, T.L.A., Dilissen, E., De Hertogh, G., Bullens, D.M.A., Ceuppens, J.L., Van Assche, G., Vermeire, S., Rutgeerts, P., Vanderleyden, J., De Keersmaecker, S.C.J. (2010). Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis. Clinical and Experimental Immunology, 162(2), 306-314. https://doi.org/10.1111/j.1365-2249.2010.04228.x
14. Corcoran, B. M., Stanton, C., Fitzgerald, G., Ross, R. P. (2008). Life Under Stress : The Probiotic Stress Response and How it may be Manipulated. Current Pharmaceutical Design, 14(14), 1382-1399. https://doi.org/10.2174/138161208784480225
15. Corr, S.C., Li, Y., Riedel, C.U., O'Toole, P.W., Hill, C., Gahan, C.G.M. (2007). Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. PNAS, 104(18), 7617-7621. https://doi.org/10.1073/pnas.0700440104
16. Delcour, J., Ferain, T., Deghorain, M., Palumbo, E., Hols, P. (1999). The biosynthesis and functionality of the cell-wall of lactic acid bacteria. Antonie van Leeuwenhoek, 76, 159-84. https://doi.org/10.1023/A:1002089722581
17. Fanning, S., Hall, L.J., Cronin, M., Zomer, A., MacSharry, J., Goulding, D., O'Connell Motherway, M., Shanahan, F., Nally, K., Dougan, G., van Sinderen, D. (2012). Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection. Proceedings of the National Academy of Sciences, 109(6), 2108-2113. https://doi.org/10.1073/pnas.1115621109
18. FAO/WHO. (2002). Guidelines for the evalution of probiotics in food. Food and Agriculture Organization of the United Nations/World Health Organization, London, Ontario. p. 413-426.
19. Fernandez, E.M., Valenti, V., Rockel, C., Hermann, C., Pot, B., Boneca, I.G., Grangette, C. (2011). Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut, 60, 1050-1059. https://doi.org/10.1136/gut.2010.232918
20. Fotiadis, C.I., Stoidis, C.N., Spyropoulos, B.G., Zografos, E.D. (2008). Role of probiotics, prebiotics and synbiotics in chemoprevention for colorectal cancer. World Journal of Gastroenterology, 14(42), 6453-6457. https://doi.org/10.3748/wjg.14.6453
21. Ganguli, K., Collado, M.C., Rautava, J., Lu, L., Satokari, R., Von Ossowski, I., Reunanen, J., De Vos, W.M., Palva, A., Isolauri, E., Salminen, S., Walker, W.A., Rautava, S. (2015). Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut. Pediatric Research, 77, 528-535. https://doi.org/10.1038/pr.2015.5
22. Girardin, S.E., Boneca, I.G., Viala, J., Chamaillard, M., Labigne, A., Thomas, G., Philpott, D.J., Sansonetti, P.J. (2003). Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. Journal of Biological Chemistry, 278, 8869-8872. https://doi.org/10.1074/jbc.C200651200
23. Gıda, Tarım ve Hayvancılık Bakanlığı (2011). Türk gıda kodeksi etiketleme yönetmeliği. http://www.resmigazete.gov.tr/eskiler/2011/12/20111229M3-7.htm (Erişim tarihi 28.01.2019)
24. Gleeson, J.P. (2017). Diet, food components and the intestinal barrier. Nutrition Bulletin, 42(2), 123-131. https://doi.org/10.1111/nbu.12260
25. Gotteland, M., Brunser, O., Cruchet, S. (2006). Systematic review: Are probiotics useful in controlling gastric colonization by Helicobacter pylori? Alimentary Pharmacology and Therapeutics, 23(8), 1077-1086. https://doi.org/10.1111/j.1365-2036.2006.02868.x
26. Guarner, F., Perdigon, G., Corthier, G., Salminen, S., Koletzko, B., Morelli, L. (2005). Should yoghurt cultures be considered probiotic? British Journal of Nutrition, 93(6), 783-786. https://doi.org/10.1079/BJN20051428
27. Gürsoy, O., Kınık, Ö., Gönen, İ. (2005). Probiyotikler ve gastrointestinal sağlığa etkileri. Türk Mikrobiyoloji Cemiyeti Dergisi, 35(2), 136-148.
28. Hafez, M., Hayes, K., Goldrick, M., Warhurst, G., Grencis, R., Roberts, I.S. (2009). The K5 capsule of Escherichia coli strain Nissle 1917 is important in mediating interactions with intestinal epithelial cells and chemokine induction. Infection and Immunity, 77(7), 2995-3003. https://doi.org/10.1128/IAI.00040-09
29. Hevia, A., Delgado, S., Sánchez, B., Margolles, A. (2015). Molecular players involved in the interaction between beneficial bacteria and the immune system. Frontiers in Microbiology, 6, 1-8. https://doi.org/10.3389/fmicb.2015.01285
30. Hirose, Y., Murosaki, S., Fujiki, T., Yamamoto, Y., Yoshikai, Y., Yamashita, M. (2010). Lipoteichoic acids on Lactobacillus plantarum cell surfaces correlate with induction of interleukin-12p40 production. Microbiology and Immunology, 54(3), 143-151. https://doi.org/10.1111/j.1348-0421.2009.00189.x
31. Hoveyda, N., Heneghan, C., Mahtani, K.R., Perera, R., Roberts, N., Glasziou, P. (2009). A systematic review and meta-analysis: Probiotics in the treatment of irritable bowel syndrome. BMC Gastroenterology, 9(15), 1-11. https://doi.org/10.1186/1471-230X-9-15
32. Hynönen, U., Palva, A. (2013). Lactobacillus surface layer proteins: Structure, function and applications. Applied Microbiology and Biotechnology, 97(12), 5225-5243. https://doi.org/10.1007/s00253-013-4962-2
33. Ivanov, D., Emonet, C., Foata, F., Affolter, M., Delley, M., Fisseha, M., Blum-Sperisen, S., Kochhar, S., Arigoni, F. (2006). A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastase-like serine proteases. Journal of Biological Chemistry, 281, 17246-17252. https://doi.org/10.1074/jbc.M601678200
34. Johnson-Henry, K.C., Hagen, K.E., Gordonpour, M., Tompkins, T.A., Sherman, P.M. (2007). Surface-layer protein extracts from Lactobacillus helveticus inhibit enterohaemorrhagic Escherichia coli O157:H7 adhesion to epithelial cells. Cellular Microbiology, 9(2), 356-367. https://doi.org/10.1111/j.1462-5822.2006.00791.x
35. Kaji, R., Kiyoshima-Shibata, J., Nagaoka, M., Nanno, M., Shida, K. (2010). Bacterial Teichoic Acids Reverse Predominant IL-12 Production Induced by Certain Lactobacillus Strains into Predominant IL-10 Production via TLR2-Dependent ERK Activation in Macrophages. The Journal of Immunology, ji_0901569, 1-9. https://doi.org/10.4049/jimmunol.0901569
36. Kalliomäki, M.A., Isolauri, E. (2004). Probiotics and down-regulation of the allergic response. Immunology and Allergy Clinics of North America, 24(4), 739-752. https://doi.org/10.1016/j.iac.2004.06.006
37. Kang, H., Im, S. (2015). Probiotics as an Immune Modulator. Journal of Nutritional Science and Vitaminology, 61, 103-105. https://doi.org/10.3177/jnsv.61.S103
38. Kawai, T., Akira, S. (2011). Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity. Immunity, 34(5), 637-650. https://doi.org/10.1016/j.immuni.2011.05.006
39. Kelesidis, T., Pothoulakis, C. (2012). Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Therapeutic Advances in Gastroenterology, 5(2), 111-125. https://doi.org/10.1177/1756283X11428502
40. Khazaie, K., Zadeh, M., Khan, M.W., Bere, P., Gounari, F., Dennis, K., Blatner, N.R., Owen, J.L., Klaenhammer, T.R., Mohamadzadeh, M. (2012). Abating colon cancer polyposis by Lactobacillus acidophilus deficient in lipoteichoic acid. Proceedings of the National Academy of Sciences, 109(26), 10462-10467. https://doi.org/10.1073/pnas.1207230109
41. Kim, H., Lee, S., Kim, N., Ko, M., Lee, J., Yi, T., Chung, S.K., Chung, D. (2008). Inhibitory effects of Lactobacillus plantarum lipoteichoic acid (LTA) on Staphylococcus aureus LTA-induced tumor necrosis factor-alpha production. Journal of Microbiology and Biotechnology, 18(6), 1191-1996.
42. Kleerebezem, M., Binda, S., Bron, P.A., Gross, G., Hill, C., van Hylckama Vlieg, J.E., Lebeer, S., Satokari, R., Ouwehand, A.C. (2019). Understanding mode of action can drive the translational pipeline towards more reliable health benefits for probiotics. Current Opinion in Biotechnology, 56, 55-60. https://doi.org/10.1016/j.copbio.2018.09.007
43. Kleerebezem, M., Hols, P., Bernard, E., Rolain, T., Zhou, M., Siezen, R.J., Bron, P.A. (2010). The extracellular biology of the lactobacilli. FEMS Microbiology Reviews, 34(2), 199-230. https://doi.org/10.1111/j.1574-6976.2009.00208.x
44. Konstantinov, S.R., Smidt, H., de Vos, W.M., Bruijns, S.C.M., Singh, S.K., Valence, F., Molle, D., Lortal, S., Altermann, E., Klaenhammer, T.R., van Kooyk, Y. (2008). S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proceedings of the National Academy of Sciences of the United States of America, 105(49), 19473-19478. https://doi.org/10.1073/pnas.0810305105
45. Krishna Rao, R., Samak, G. (2013). Protection and Restitution of Gut Barrier by Probiotics: Nutritional and Clinical Implications. Current Nutrition and Food Science, 9(2), 99-107. https://doi.org/10.2174/1573401311309020004
46. Kumar, H., Kawai, T., Akira, S. (2011). Pathogen Recognition by the Innate Immune System. International Reviews of Immunology, 30(1), 16-34. https://doi.org/10.3109/08830185.2010.529976
47. Kumar, M., Kumar, A., Nagpal, R., Mohania, D., Behare, P., Verma, V., Kumar, P., Poddar, D., Aggarwal, P.K., Henry, C.J.K., Jain, S., Yadav, H. (2010). Cancer-preventing attributes of probiotics: An update. International Journal of Food Sciences and Nutrition, 61(5), 473-496. https://doi.org/10.3109/09637480903455971
48. Kumar, H., Kawai, T., Shizuo, A. (2009). Toll-like receptors and innate immunity. Biochemical and Biophysical Research Communications, 388(4), 621-625. https://doi.org/10.1016/j.bbrc.2009.08.062
49. Lebeer, S., Claes, I., Tytgat, H.L.P., Verhoeven, T.L.A., Marien, E., von Ossowski, I., Reunanen, J., Palva, A., de Vos, W.M., De Keersmaecker, S.C.J., Vanderleyden, J. (2012). Functional analysis of lactobacillus rhamnosus GG pili in relation to adhesion and immunomodulatory interactions with intestinal epithelial cells. Applied and Environmental Microbiology, 78(1), 185-193. https://doi.org/10.1128/AEM.06192-11
50. Lebeer, S., Claes, I.J.J., Verhoeven, T.L.A., Vanderleyden, J., De Keersmaecker, S.C.J. (2011). Exopolysaccharides ofLactobacillus rhamnosusGGform a protective shield against innate immunefactors in the intestine. Microbial Biotechnology, 4(3), 368-374. https://doi.org/10.1111/j.1751-7915.2010.00199.x
51. Lebeer, S., Vanderleyden, J., De Keersmaecker, S.C.J. (2008). Genes and Molecules of Lactobacilli Supporting Probiotic Action. Microbiology and Molecular Biology Reviews, 72(4), 728-764. https://doi.org/10.1128/MMBR.00017-08
52. Lee, I.C., Tomita, S., Kleerebezem, M., Bron, P.A. (2013). The quest for probiotic effector molecules - Unraveling strain specificity at the molecular level. Pharmacological Research, 69(1), 61-74. https://doi.org/10.1016/j.phrs.2012.09.010
53. Lightfoot, Y.L., Selle, K., Yang, T., Goh, Y.J., Sahay, B., Zadeh, M., Owen, J.L., Colliou, N., Li, E., Johannssen, T., Lepenies, B., Klaenhammer, T.R., Mohamadzadeh, M. (2015). SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. The EMBO Journal, 34(7), 881-895. https://doi.org/10.15252/embj.201490296
54. Macfarlane, G.T., Cummings, J.H. (2002). Probiotics, Infection and Immunity. Current Opinion in Infectious Diseases, 15(5), 501-506. https://doi.org/10.1097/00001432-200210000-00008
55. Matsuguchi, T., Takagi, A., Matsuzaki, T., Nagaoka, M., Ishikawa, K., Yokokura, T., Yoshikai, Y. (2003). Lipoteichoic Acids from Lactobacillus Strains Elicit Strong Tumor Necrosis Factor Alpha-Inducing Activities in Macrophages through Toll-Like Receptor 2. Clinical and Diagnostic Laboratory Immunology, 10(2), 259-266. https://doi.org/10.1128/CDLI.10.2.259-266.2003
56. Matsuki, T., Pe, T. (2013). Epithelial Cell Proliferation Arrest Induced by Lactate and Acetate from Lactobacillus casei and Bifidobacterium breve. PLoS One, 8(4), 1-8. https://doi.org/10.1371/journal.pone.0063053
57. Matsumoto, S., Hara, T., Hori, T., Mitsuyama, K., Nagaoka, M., Tomiyasu, N., Suzuki, A., Sata, M. (2005). Probiotic Lactobacillus-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines in lamina propria mononuclear cells. Clinical and Experimental Immunology, 140(3), 417-426. https://doi.org/10.1111/j.1365-2249.2005.02790.x
58. McFarland, L.V. (2006). Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. American Journal of Gastroenterology, 101, 812-822. https://doi.org/10.1111/j.1572-0241.2006.00465.x
59. Meijerink, M., Van Hemert, S., Taverne, N., Wels, M., de Vos, P., Bron, P.A., Savelkoul, F., van Bilsen, J., Kleerebezem, M., Wells, J.M. (2010). Identification of genetic loci in Lactobacillus plantarum that modulate the immune response of dendritic cells using comparative genome hybridization. PLoS One, 5(5), e10632. https://doi.org/10.1371/journal.pone.0010632
60. Melmed, G., Thomas, L.S., Lee, N., Tesfay, S.Y., Lukasek, K., Michelsen, K.S., Zhou, Y., Hu, B., Arditi, M., Abreu, M.T. (2003). Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut. The Journal of Immunology, 170(3), 1406-1415. https://doi.org/10.4049/jimmunol.170.3.1406
61. Meng, J., Zhu, X., Gao, S.M., Zhang, Q.X., Sun, Z., Lu, R.R. (2014). Characterization of surface layer proteins and its role in probiotic properties of three Lactobacillus strains. International Journal of Biological Macromolecules, 65, 110-114. https://doi.org/10.1016/j.ijbiomac.2014.01.024
62. Mohamadzadeh, M., Pfeiler, E.A., Brown, J.B., Zadeh, M., Gramarossa, M., Managlia, E., Bere, P., Sarraj, B., Khan, M.W., Pakanati, K.C., Ansari, M.J., O'Flaherty, S., Barrett, T., Klaenhammer, T.R. (2011). Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid. PNAS, 108(1), 4623-4630. https://doi.org/10.1073/pnas.1005066107
63. Mozzi, F., Gerbino, E., Font De Valdez, G., Torino, M.I. (2009). Functionality of exopolysaccharides produced by lactic acid bacteria in an in vitro gastric system. Journal of Applied Microbiology, 107(1), 56-64. https://doi.org/10.1111/j.1365-2672.2009.04182.x
64. Murofushi, Y., Villena, J., Morie, K., Kanmani, P., Tohno, M., Shimazu, T., Aso, H., Suda, Y., Hashiguchi, K., Saito, T., Kitazawa, H. (2015). The toll-like receptor family protein RP105/MD1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14. Molecular Immunology, 64(1), 63-75. https://doi.org/10.1016/j.molimm.2014.10.027
65. Nagpal, R., Yadav, H., Kumar, M., Jain, S., Yamashiro, Y., Marotta, F. (2014). Probiotics, Prebiotics and Synbiotics: An Introduction. İçinde S. Ötleş (Eds.). Probiotics and Prebiotics in Food, Nutrition and Health (s. 1-24). Boca Raton: Taylor & Francis Group. ISNB 13: 978-1-4665-8624-6 https://doi.org/10.1201/b15561-2
66. Neuhaus, F. C., Baddiley, J. (2003). A Continuum of Anionic Charge: Structures and Functions of D-Alanyl-Teichoic Acids in Gram-Positive Bacteria. Microbiology and Molecular Biology Reviews, 67(4), 686-723. https://doi.org/10.1128/MMBR.67.4.686-723.2003
67. Ogura, Y., Bonen, D.K., Inohara, N., Nicolae, D.L., Chen, F.F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerrk, R.H., Achkar, J.-P., Brant, S.R., Bayless, T.M., Kirschner, B.S., Hanauer, S,B., Nuñez, G.N., Cho, J.H. (2001). A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature, 411, 603-606. https://doi.org/10.1038/35079114
68. Otte, J.M., Podolsky, D.K. (2004). Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. American Journal of Physiology-Gastrointestinal and Liver Physiology, 286(4), G613-G626. https://doi.org/10.1152/ajpgi.00341.2003
69. Ouwehand, A.C., Salminen, S., Isolauri, E. (2002). Probiotics : an overview of beneficial effects. Antonie van Leeuwenhoek, 82, 279-289. https://doi.org/10.1023/A:1020620607611
70. Pandey, K.R., Naik, S.R., Vakil, B.V. (2015). Probiotics, prebiotics and synbiotics- a review. Association of Food Scientists and Technologists, 52(12), 7577-7587. https://doi.org/10.1007/s13197-015-1921-1
71. Parvez, S., Malik, K.A., Ah Kang, S., Kim, H.Y. (2006). Probiotics and their fermented food products are beneficial for health. Journal of Applied Microbiology, 100(6), 1171-1185. https://doi.org/10.1111/j.1365-2672.2006.02963.x
72. Rafter, J. (2002). Lactic acid bacteria and cancer: mechanistic perspective. British Journal of Nutrition, 88(1), 89-94. https://doi.org/10.1079/BJN2002633
73. Reunanen, J., von Ossowski, I., Hendrickx, A.P.A., Palva, A., de Vosa, W.M. (2012). Characterization of the SpaCBA pilus fibers in the probiotic Lactobacillus rhamnosus GG. Applied and Environmental Microbiology, 78(7), 2337-2344. https://doi.org/10.1128/AEM.07047-11
74. Rodgers, S. (2008). Novel applications of live bacteria in food services: probiotics and protective cultures. Trends in Food Science and Technology, 19(4), 188-197. https://doi.org/10.1016/j.tifs.2007.11.007
75. Ruas-Madiedo, P., Medrano, M., Salazar, N., De Los Reyes-Gavilán, C.G., Pérez, P.F., Abraham, A.G. (2010). Exopolysaccharides produced by Lactobacillus and Bifidobacterium strains abrogate in vitro the cytotoxic effect of bacterial toxins on eukaryotic cells. Journal of Applied Microbiology, 109(6), 2079-2086. https://doi.org/10.1111/j.1365-2672.2010.04839.x
76. Ruiz, L., Hevia, A., Bernardo, D., Margolles, A., Sánchez, B. (2014). Extracellular molecular effectors mediating probiotic attributes. FEMS Microbiology Letters, 359(1), 1-11. https://doi.org/10.1111/1574-6968.12576
77. Rupa, P., Mine, Y. (2012). Recent advances in the role of probiotics in human In flammation and gut health. Journal of Agricultural and Food Chemistry, 60(34), 8249-8256. https://doi.org/10.1021/jf301903t
78. Saber, R., Zadeh, M., Pakanati, K.C., Bere, P., Klaenhammer, T., Mansour, M. (2011). Lipoteichoic acid-deficient Lactobacillus acidophilus regulates downstream signals. Immunotherapy, 3(3), 337-347. https://doi.org/10.2217/imt.10.119
79. Sağdıç, O., Küçüköner, E., Özçelik, S. (2004). Probiyotik ve Prebiyotiklerin Fonksiyonel Özellikleri. Atatürk Üniversitesi Ziraat Fakültesi Dergisi, 35(3-4), 221-228.
80. Sarkar, A., Mandal, S. (2016). Bifidobacteria-Insight into clinical outcomes and mechanisms of its probiotic action. Microbiological Research, 192, 159-171. https://doi.org/10.1016/j.micres.2016.07.001
81. Sarkar, S. (2013). Probiotics as functional foods: gut colonization and safety concerns. Nutrition and Food Science, 43(5), 496-504. https://doi.org/10.1108/NFS-10-2011-0120
82. Schell, M.A., Karmirantzou, M., Snel, B., Vilanova, D., Berger, B., Pessi, G., Zwahlen, M.-C., Desiere, F., Bork, P., Delley, M., Pridmore, R.D., Arigoni, F. (2002). The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proceedings of the National Academy of Sciences, 99(22), 14422-14427. https://doi.org/10.1073/pnas.212527599
83. Schlee, M., Harder, J., Köten, B., Stange, E.F., Wehkamp, J., Fellermann, K. (2008). Probiotic lactobacilli and VSL#3 induce enterocyte β-defensin 2. Clinical and Experimental Immunology, 151(3), 528-535. https://doi.org/10.1111/j.1365-2249.2007.03587.x
84. Schlee, M., Wehkamp, J., Altenhoefer, A., Oelschlaeger, T.A., Stange, E.F., Fellermann, K. (2007). Induction of human β-defensin 2 by the probiotic Escherichia coli Nissle 1917 is mediated through flagellin. Infection and Immunity, 75(5), 2399-2407. https://doi.org/10.1128/IAI.01563-06
85. Seth, A., Yan, F., Polk, D.B., Rao, R.K. (2008). Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism. American Journal of Physiology-Gastrointestinal and Liver Physiology, 294(4), 1060-1069. https://doi.org/10.1152/ajpgi.00202.2007
86. Sheil, B., Shanahan, F., O'Mahony, L. (2007). Probiotic effects on inflammatory bowel disease. The Journal of Nutrition, 137(3), 819-824. https://doi.org/10.1093/jn/137.3.819S
87. Shida, K., Kiyoshima-Shibata, J., Kaji, R., Nagaoka, M., Nanno, M. (2009). Peptidoglycan from lactobacilli inhibits interleukin-12 production by macrophages induced by Lactobacillus casei through Toll-like receptor 2-dependent and independent mechanisms. Immunology, 128(1pt2), 858-869. https://doi.org/10.1111/j.1365-2567.2009.03095.x
88. Singh, K., Kallali, B., Kumar, A., Thaker, V. (2011). Probiotics: A review. Asian Pacific Journal of Tropical Biomedicine, 1(2), 287-290. https://doi.org/10.1016/S2221-1691(11)60174-3
89. Sudha, R.M., Bhonagiri, S. (2012). Efficacy of Bacillus Coagulans Strain Unique Is-2 in the Treatment of Patients With Acute Diarrhea. International Journal of Probiotics and Prebiotics, 7(1), 33-37.
90. Tabasco, R., Fernández, P., Palencia, D., Fontecha, J., Peláez, C., Requena, T. (2014). Competition mechanisms of lactic acid bacteria and bi fi dobacteria : Fermentative metabolism and colonization. LWT - Food Science and Technology, 55(2), 680-684. https://doi.org/10.1016/j.lwt.2013.10.004
91. Tanaka, Y., Kanazawa, M., Fukudo, S., Drossman, D.A. (2011). Biopsychosocial model of irritable bowel syndrome. Journal of Neurogastroenterology and Motility, 17(2), 131-139. https://doi.org/10.5056/jnm.2011.17.2.131
92. Tsilingiri, K., Rescigno, M. (2013). Postbiotics : what else ?. Beneficial Microbes, 4(1), 101-107. https://doi.org/10.3920/BM2012.0046
93. Turroni, F., Serafini, F., Foroni, E., Duranti, S., O'Connell Motherway, M., Taverniti, V., Mangifesta, M., Milani, C., Viappiani, A., Roversi, T., Sánchez, B., Santoni, A., Gioiosa, L., Ferrarini, A., Delledonne, M., Margolles, A., Piazza, L., Palanza, P., Bolchi, A., Guglielmetti, S., van Sinderen, D., Ventura, M. (2013). Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions. Proceedings of the National Academy of Sciences of the United States of America, 110(27), 11151-11156. https://doi.org/10.1073/pnas.1303897110
94. Tytgat, H.L.P., Douillard, F.P., Reunanen, J., Rasinkangas, P., Hendrickx, A.P.A., Laine, P.K., Paulin, L., Satokari, R., Vos, W.M. de. (2016). Lactobacillus rhamnosus GG Outcompetes Enterococcus faecium via Mucus-Binding Pili: Evidence for a Novel and Heterospecific Probiotic Mechanism. Applied and Environmental Microbiology, 82(19), 5756-5762. https://doi.org/10.1128/AEM.01243-16
95. Van Hemert, S., Meijerink, M., Molenaar, D., Bron, P. A., De Vos, P., Kleerebezem, M., Wells, J., M. Marco, M. L. (2010). Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells. BMC Microbiology, 10(293), 1-13. https://doi.org/10.1186/1471-2180-10-293
96. Vargas García, C.E., Petrova, M., Claes, I.J.J., De Boeck, I., Verhoeven, T.L.A., Dilissen, E., Von Ossowski, I., Palva, A., Bullens, D.M., Vanderleyden, J., Lebeer, S. (2015). Piliation of Lactobacillus rhamnosus GG promotes adhesion, phagocytosis, and cytokine modulation in macrophages. Applied and Environmental Microbiology, 81(6), 2050-2062. https://doi.org/10.1128/AEM.03949-14
97. Veerappan, G.R., Betteridge, J., Young, P.E. (2012). Probiotics for the treatment of inflammatory bowel disease. Current Gastroenterology Reports, 14(4), 324-333. https://doi.org/10.1007/s11894-012-0265-5
98. Vidal, K., Donnet-Hughes, A., Granato, D. (2002). Lipoteichoic Acids from Lactobacillus johnsonii Strain La1 and Lactobacillus acidophilus Strain La10 Antagonize the Responsiveness of Human Intestinal Epithelial HT29 Cells to Lipopolysaccharide and Gram-Negative Bacteria. Infection and Immunity, 70(4), 2057-2064. https://doi.org/10.1128/IAI.70.4.2057-2064.2002
99. Villena, J., Alvarez, S., Kitazawa, H. (2013). Introduction. İçinde Kitazawa, H., Villena, J. ve Alvarez, S. (Eds.), Probiotics: Immunobiotica And Immunogenics (s. 1-11). Boca Raton: Taylor & Francis Group. ISNB 978-1-4822-0685-2 https://doi.org/10.1201/b15532-2
100. Von Schillde, M.A., Hörmannsperger, G., Weiher, M., Alpert, C.A., Hahne, H., Bäuerl, C., Van Huynegem, K., Steidler, L., Hrncir, T., Pérez-Martínez, G., Kuster, B., Haller, D. (2012). Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines. Cell Host and Microbe, 11(4), 387-396. https://doi.org/10.1016/j.chom.2012.02.006
101. Wu, M.H., Tzu-Ming P., Yu-Jen, W., Chang, S.J., Chang, M.S., Hu, C.Y. (2010). Exopolysaccharide activities from probiotic bifidobacterium: Immunomodulatory effects (on J774A.1 macrophages) and antimicrobial properties. International Journal of Food Microbiology, 144(1), 104-110. https://doi.org/10.1016/j.ijfoodmicro.2010.09.003
102. Yan, F., Liu, L., Dempsey, P.J., Tsai, Y.H., Raines, E.W., Wilson, C.L., Cao, H., Cao, Z., Liu, L., Polk, D.B. (2013). A lactobacillus rhamnosus GG-derived soluble protein, p40, stimulates ligand release from intestinal epithelial cells to transactivate epidermal growth factor receptor. Journal of Biological Chemistry, 288(42), 30742-30751. https://doi.org/10.1074/jbc.M113.492397
103. Yan, F., Cao, H., Cover, T.L., Whitehead, R., Washington, M.K., Polk, D.B. (2007). Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell sur vival and growth. Gastroenterology, 132(2), 562-575. https://doi.org/10.1053/j.gastro.2006.11.022
104. Yasuda, E., Serata, M., Sako, T. (2008). Suppressive effect on activation of macrophages by Lactobacillus casei strain shirota genes determining the synthesis of cell wall-associated polysaccharides. Applied and Environmental Microbiology, 74(15), 4746-4755. https://doi.org/10.1128/AEM.00412-08