The microbiota and health promoting characteristics of the fermented beverage kefir

Frontiers in Microbiology

Volumn 7, Issue MAY, 2016, Pages

  Bourrie, Benjamin C T ^a,b   Willing, Benjamin P ^a   Cotter, Paul D ^b,c  

^a UNIVERSITY OF ALBERTA   (Canada)

^b TEAGASC FOOD RESEARCH CENTRE   (Ireland)

^c UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

Fermented foods; Gut microbiota; Immunomodulation; Kefir; Metabolic diseases

Indexed keywords

CXCL2 CHEMOKINE; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 6; INTERLEUKIN 8; KEFIR; TUMOR NECROSIS FACTOR ALPHA;

ALLERGENICITY; ANTIMICROBIAL ACTIVITY; BEVERAGE; BIFIDOBACTERIUM BIFIDUM; CANCER INHIBITION; CARDIOVASCULAR DISEASE ASSESSMENT; CONTROLLED STUDY; DISK DIFFUSION; ESCHERICHIA COLI; HEALTH PROMOTION; IMMUNE SYSTEM; IMMUNOMODULATION; LACTOBACILLUS; MICROFLORA; NONHUMAN; REVIEW; SEQUENCE ANALYSIS; STREPTOCOCCACEAE; WOUND HEALING;

EID: 84973449038     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2016.00647     Document Type: Review

References (128)

1. Altmann, S. W., Davis, H. R. Jr., Zhu, L. J., Yao, X., Hoos, L. M., Tetzloff, G., et al. (2004). Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 303, 1201-1204. doi: 10.1126/science.1093131
2. Angulo, L., Lopez, E., and Lema, C. (1993). Microflora present in kefir grains of the Galician region (North-West of Spain). J. Dairy Res. 60, 263-267. doi: 10.1017/S002202990002759X
3. Assadi, M. M., Pourahmad, R., and Moazami, N. (2000). Use of isolated kefir starter cultures in kefir production. World J. Microbiol. Biotechnol. 16, 541-543. doi: 10.1023/A:1008939132685
4. Atalan, G., Demirkan, I., Yaman, H., and Cina, M. (2003). Effect of topical kefir application on open wound healing on in vivo study. Kafkas Univ. Vet. Fak. Dderg. 9, 43-47.
5. Azad, M. B., Konya, T., Maughan, H., Guttman, D. S., Field, C. J., Sears, M. R., et al. (2013). Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity. Allergy Asthma Clin. Immunol. 9, 15. doi: 10.1186/1710-1492-9-15
6. Beena, A., and Prasad, V. (1997). Effect of yogurt and bifidus yogurt fortified with skim milk powder, condensed whey and lactose-hydrolysed condensed whey on serum cholesterol and triacylglycerol levels in rats. J. Dairy Res. 64, 453-457. doi: 10.1017/S0022029997002252
7. Buts, J.-P., De Keyser, N., and De Raedemaeker, L. (1994). Saccharomyces boulardii enhances rat intestinal enzyme expression by endoluminal release of polyamines. Pediatr. Res. 36, 522-527. doi: 10.1203/00006450-199410000-00019
8. Carasi, P., Racedo, S., Jacquot, C., Romanin, D., Serradell, M., and Urdaci, M. (2015). Impact of Kefir Derived Lactobacillus kefiri on the mucosal immune response and gut microbiota. J. Immunol. Res. 2015, 361604. doi: 10.1155/2015/361604
9. Castagliuolo, I., Riegler, M. F., Valenick, L., LaMont, J. T., and Pothoulakis, C. (1999). Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect. Immun. 67, 302-307.
10. Cevikbas, A., Yemni, E., Ezzedenn, F. W., Yardimici, T., Cevikbas, U., and Stohs, S. (1994). Antitumoural antibacterial and antifungal activities of kefir and kefir grain. Phytother. Res. 8, 78-82. doi: 10.1002/ptr.2650080205
11. Chen, H.-C., Wang, S.-Y., and Chen, M.-J. (2008). Microbiological study of lactic acid bacteria in kefir grains by culture-dependent and culture-independent methods. Food Microbiol. 25, 492-501. doi: 10.1016/j.fm.2008.01.003
12. Chen, Y., Hsiao, P., Hong, W., Dai, T., and Chen, M. (2012). Lactobacillus kefiranofaciens M1 isolated from milk kefir grains ameliorates experimental colitis in vitro and in vivo. J. Dairy Sci. 95, 63-74. doi: 10.3168/jds.2011-4696
13. Chen, Y., Lee, T., Hong, W., Hsieh, H., and Chen, M. (2013). Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on enterohemorrhagic Escherichia coli infection using mouse and intestinal cell models. J. Dairy Sci. 96, 7467-7477. doi: 10.3168/jds.2013-7015
14. Chen, Y.-P., and Chen, M.-J. (2013). Effects of Lactobacillus kefiranofaciens M1 Isolated from kefir grains on germ-free mice. PLoS ONE 8:e78789. doi: 10.1371/journal.pone.0078789
15. Correa Franco, M., Golowczyc, M. A., De Antoni, G. L., Pérez, P. F., Humen, M., and de los Angeles Serradell, M. (2013). Administration of kefir-fermented milk protects mice against Giardia intestinalis infection. J. Med. Microbiol 62, 1815-1822. doi: 10.1099/jmm.0.068064-0
16. Corthier, G., Dubos, F., and Ducluzeau, R. (1986). Prevention of Clostridium difficile induced mortality in gnotobiotic mice by Saccharomyces boulardii. Can. J. Microbiol. 32, 894-896. doi: 10.1139/m86-164
17. Czerucka, D., Piche, T., and Rampal, P. (2007). Review article: yeast as probiotics-Saccharomyces boulardii. Aliment. Pharmacol. Ther. 26, 767-778. doi: 10.1111/j.1365-2036.2007.03442.x
18. de Moreno de LeBlanc, A., Matar, C., Farnworth, E., and Perdigon, G. (2006). Study of cytokines involved in the prevention of a murine experimental breast cancer by kefir. Cytokine 34, 1-8. doi: 10.1016/j.cyto.2006.03.008
19. de Moreno de LeBlanc, A., Matar, C., Farnworth, E., and Perdigon, G. (2007). Study of immune cells involved in the antitumor effect of kefir in a murine breast cancer model. J. Dairy Sci. 90, 1920-1928. doi: 10.3168/jds.2006-079
20. Diosma, G., Romanin, D. E., Rey-Burusco, M. F., Londero, A., and Garrote, G. L. (2014). Yeasts from kefir grains: isolation, identification, and probiotic characterization. World J. Microbiol. Biotechnol. 30, 43-53. doi: 10.1007/s11274-013-1419-9
21. Dobson, A., O'Sullivan, O., Cotter, P. D., Ross, P., and Hill, C. (2011). High-throughput sequence-based analysis of the bacterial composition of kefir and an associated kefir grain. FEMS Microbiol. Lett. 320, 56-62. doi: 10.1111/j.1574-6968.2011.02290.x
22. Frengova, G. I., Simova, E. D., Beshkova, D. M., and Simov, Z. I. (2002). Exopolysaccharides produced by lactic acid bacteria of kefir grains. Z. Naturforsch. C 57, 805-810.
23. Gao, J., Gu, F., Ruan, H., Chen, Q., He, J., and He, G. (2013). Induction of apoptosis of gastric cancer cells SGC7901 in vitro by a cell-free fraction of Tibetan kefir. Int. Dairy J. 30, 14-18. doi: 10.1016/j.idairyj.2012.11.011
24. Garofalo, C., Osimani, A., Milanovic, V., Aquilanti, L., De Filippis, F., Stellato, G., et al. (2015). Bacteria and yeast microbiota in milk kefir grains from different Italian regions. Food Microbiol. 49, 123-133. doi: 10.1016/j.fm.2015.01.017
25. Garrote, G. L., Abraham, A. G., and De Antoni, G. L. (2001). Chemical and microbiological characterisation of kefir grains. J. Dairy Res. 68, 639-652. doi: 10.1017/S0022029901005210
26. Ghoneum, M., and Gimzewski, J. (2014). Apoptotic effect of a novel kefir product, PFT, on multidrug-resistant myeloid leukemia cells via a hole-piercing mechanism. Int. J. Oncol. 44, 830-837. doi: 10.3892/ijo.2014.2258
27. Golowczyc, M. A., Gugliada, M. J., Hollmann, A., Delfederico, L., Garrote, G. L., Abraham, A. G., et al. (2008). Characterization of homofermentative Lactobacilli isolated from kefir grains: potential use as probiotic. J. Dairy Res. 75, 211-217. doi: 10.1017/S0022029908003117
28. Güzel-Seydim, Z., Seydim, A., Greene, A., and Bodine, A. (2000). Determination of organic acids and volatile flavor substances in kefir during fermentation. J. Food Composit. Anal. 13, 35-43. doi: 10.1006/jfca.1999.0842
29. Guzel-Seydim, Z., Seydim, A., Greene, A., and Tas, T. (2006). Determination of antimutagenic properties of acetone extracted fermented milks and changes in their total fatty acid profiles including conjugated linoleic acids. Int. J. Dairy Technol. 59, 209-215. doi: 10.1111/j.1471-0307.2006.00265.x
30. Hamet, M. F., Londero, A., Medrano, M., Vercammen, E., Van Hoorde, K., Garrote, G. L., et al. (2013). Application of culture-dependent and culture-independent methods for the identification of Lactobacillus kefiranofaciens in microbial consortia present in kefir grains. Food Microbiol. 36, 327-334. doi: 10.1016/j.fm.2013.06.022
31. Hamet, M. F., Medrano, M., Pérez, P. F., and Abraham, A. G. (2016). Oral administration of kefiran exerts a bifidogenic effect on BALB/c mice intestinal microbiota. Benef. Microbes 7, 237-246. doi: 10.3920/BM2015.0103
32. Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., et al. (2014). Expert consensus document: the international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11, 506-514. doi: 10.1038/nrgastro.2014.66
33. Hong, W.-S., Chen, H.-C., Chen, Y.-P., and Chen, M.-J. (2009). Effects of kefir supernatant and lactic acid bacteria isolated from kefir grain on cytokine production by macrophage. Int. Dairy J. 19, 244-251. doi: 10.1016/j.idairyj.2008.10.010
34. Hong, W.-S., Chen, Y.-P., and Chen, M.-J. (2010). The antiallergic effect of kefir Lactobacilli. J. Food Sci. 75, H244-H253. doi: 10.1111/j.1750-3841.2010.01787.x
35. Hong, W.-S., Chen, Y.-P., Dai, T.-Y., Huang, I.-N., and Chen, M.-J. (2011). Effect of heat-inactivated kefir-isolated Lactobacillus kefiranofaciens M1 on preventing an allergic airway response in mice. J. Agric. Food Chem. 59, 9022-9031. doi: 10.1021/jf201913x
36. Huang, Y., Wang, X., Wang, J., Wu, F., Sui, Y., Yang, L., et al. (2013a). Lactobacillus plantarum strains as potential probiotic cultures with cholesterol-lowering activity. J. Dairy Sci. 96, 2746-2753. doi: 10.3168/jds.2012-6123
37. Huang, Y., Wu, F., Wang, X., Sui, Y., Yang, L., and Wang, J. (2013b). Characterization of Lactobacillus plantarum Lp27 isolated from tibetan kefir grains: a potential probiotic bacterium with cholesterol-lowering effects. J. Dairy Sci. 96, 2816-2825. doi: 10.3168/jds.2012-6371
38. Hugo, A., Kakisu, E., De Antoni, G., and Perez, P. (2008). Lactobacilli antagonize biological effects of enterohaemorrhagic Escherichia coli in vitro. Lett. Appl. Microbiol. 46, 613-619. doi: 10.1111/j.1472-765X.2008.02363.x
39. Huseini, H. F., Rahimzadeh, G., Fazeli, M. R., Mehrazma, M., and Salehi, M. (2012). Evaluation of wound healing activities of kefir products. Burns 38, 719-723. doi: 10.1016/j.burns.2011.12.005
40. Iraporda, C., Romanin, D. E., Rumbo, M., Garrote, G. L., and Abraham, A. G. (2014). The role of lactate on the immunomodulatory properties of the nonbacterial fraction of kefir. Food Res. Int. 62, 247-253. doi: 10.1016/j.foodres.2014.03.003
41. Ismail, A. A., El-Nockrashy, S. A., and Khorshid, M. (1983). A beverage from separated buffalo milk fermented with kefir grains. Int. J. Dairy Technol. 36, 117-118. doi: 10.1111/j.1471-0307.1983.tb02230.x
42. Kakisu, E., Abraham, A. G., Tironi Farinati, C., Ibarra, C., and De Antoni, G. L. (2013). Lactobacillus plantarum isolated from kefir protects vero cells from cytotoxicity by type-II shiga toxin from Escherichia coli O157: H7. J. Dairy Res. 80, 64-71. doi: 10.1017/S0022029912000659
43. Kakisu, E. J., Abraham, A. G., Perez, P. F., and De Antoni, G. L. (2007). Inhibition of Bacillus cereus in milk fermented with kefir grains. J. Food Protect. 70, 2613-2616.
44. Kirjavainen, P., Arvola, T., Salminen, S., and Isolauri, E. (2002). Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning? Gut 51, 51-55. doi: 10.1136/gut.51.1.51
45. Korsak, N., Taminiau, B., Leclercq, M., Nezer, C., Crevecoeur, S., Ferauche, C., et al. (2015). Short communication: evaluation of the microbiota of kefir samples using metagenetic analysis targeting the 16S and 26S ribosomal DNA fragments. J. Dairy Sci. 98, 3684-3689. doi: 10.3168/jds.2014-9065
46. Kotowska, M., Albrecht, P., and Szajewska, H. (2005). Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial. Aliment. Pharmacol. Ther. 21, 583-590. doi: 10.1111/j.1365-2036.2005.02356.x
47. Kwon, O.-K., Ahn, K.-S., Lee, M.-Y., Kim, S.-Y., Park, B.-Y., Kim, M.-K., et al. (2008). Inhibitory effect of kefiran on ovalbumin-induced lung inflammation in a murine model of asthma. Arch. Pharm. Res. 31, 1590-1596. doi: 10.1007/s12272-001-2156-4
48. La Rivière, J., Kooiman, P., and Schmidt, K. (1967). Kefiran, a novel polysaccharide produced in the kefir grain by Lactobacillus brevis. Arch. Mikrobiol. 59, 269-278. doi: 10.1007/BF00406340
49. Latorre-García, L., del Castillo-Agudo, L., and Polaina, J. (2007). Taxonomical classification of yeasts isolated from kefir based on the sequence of their ribosomal RNA genes. World J. Microbiol. Biotechnol. 23, 785-791. doi: 10.1007/s11274-006-9298-y
50. Lee, M.-Y., Ahn, K.-S., Kwon, O.-K., Kim, M.-J., Kim, M.-K., Lee, I.-Y., et al. (2007). Anti-inflammatory and anti-allergic effects of kefir in a mouse asthma model. Immunobiology 212, 647-654. doi: 10.1016/j.imbio.2007.05.004
51. Leite, A., Miguel, M., Peixoto, R., Ruas-Madiedo, P., Paschoalin, V., Mayo, B., et al. (2015). Probiotic potential of selected lactic acid bacteria strains isolated from Brazilian kefir grains. J. Dairy Sci. 98, 3622-3632. doi: 10.3168/jds.2014-9265
52. Leite, A. M. O., Mayo, B., Rachid, C. T. C. C., Peixoto, R. S., Silva, J. T., Paschoalin, V. M. F., et al. (2012). Assessment of the microbial diversity of Brazilian kefir grains by PCR-DGGE and pyrosequencing analysis. Food Microbiol. 31, 215-221. doi: 10.1016/j.fm.2012.03.011
53. Li, L., Wieme, A., Spitaels, F., Balzarini, T., Nunes, O. C., Manaia, C. M., et al. (2014). Acetobacter sicerae sp. nov., isolated from cider and kefir, and identification of species of the genus Acetobacter by dnaK, groEL and rpoB sequence analysis. Int. J. Syst. Evol. Microbiol. 64, 2407-2415. doi: 10.1099/ijs.0.058354-0
54. Likotrafiti, E., Valavani, P., Argiriou, A., and Rhoades, J. (2015). In vitro evaluation of potential antimicrobial synbiotics using Lactobacillus kefiri isolated from kefir grains. Int. Dairy J. 45, 23-30. doi: 10.1016/j.idairyj.2015.01.013
55. Liu, H., Xie, Y. H., Xiong, L. X., Dong, R. T., Pan, C. L., Teng, G. X., et al. (2012). Effect and (mechanism) of cholesterol-lowering by kluyveromyces from tibetan kefir. Adv. Mater. Res. 343-344, 1290-1298.
56. Liu, J.-R., Wang, S.-Y., Chen, M.-J., Chen, H.-L., Yueh, P.-Y., and Lin, C.-W. (2006a). Hypocholesterolaemic effects of milk-kefir and soyamilk-kefir in cholesterol-fed hamsters. Br. J. Nutr. 95, 939-946. doi: 10.1079/BJN20061752
57. Liu, J. R., Wang, S. Y., Chen, M. J., Yueh, P. Y., and Lin, C. W. (2006b). The anti-allergenic properties of milk kefir and soymilk kefir and their beneficial effects on the intestinal microflora. J. Sci. Food Agric. 86, 2527-2533. doi: 10.1002/jsfa.2649
58. Maalouf, K., Baydoun, E., and Rizk, S. (2011). Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes. Cancer Manag. Res. 3:39. doi: 10.2147/CMR.S15109
59. Maccaferri, S., Klinder, A., Brigidi, P., Cavina, P., and Costabile, A. (2012). Potential probiotic Kluyveromyces marxianus B0399 modulates the immune response in Caco-2 cells and peripheral blood mononuclear cells and impacts the human gut microbiota in an in vitro colonic model system. Appl. Environ. Microbiol. 78, 956-964. doi: 10.1128/AEM.06385-11
60. Maeda, H., Zhu, X., Omura, K., Suzuki, S., and Kitamura, S. (2004a). Effects of an exopolysaccharide (kefiran) on lipids, blood pressure, blood glucose, and constipation. Biofactors 22, 197-200. doi: 10.1002/biof.5520220141
61. Maeda, H., Zhu, X., Suzuki, S., Suzuki, K., and Kitamura, S. (2004b). Structural characterization and biological activities of an exopolysaccharide kefiran produced by Lactobacillus kefiranofaciens WT-2BT. J. Agric. Food Chem. 52, 5533-5538. doi: 10.1021/jf049617g
62. Mainville, I., Robert, N., Lee, B., and Farnworth, E. R. (2006). Polyphasic characterization of the lactic acid bacteria in kefir. Syst. Appl. Microbiol. 29, 59-68. doi: 10.1016/j.syapm.2005.07.001
63. Marquina, D., Santos, A., Corpas, I., Munoz, J., Zazo, J., and Peinado, J. (2002). Dietary influence of kefir on microbial activities in the mouse bowel. Lett. Appl. Microbiol. 35, 136-140. doi: 10.1046/j.1472-765X.2002.01155.x
64. Marsh, A. J., O'Sullivan, O., Hill, C., Ross, R. P., and Cotter, P. D. (2013). Sequencing-based analysis of the bacterial and fungal composition of kefir grains and milks from multiple sources. PLoS ONE 8:e69371. doi: 10.1371/journal.pone.0069371
65. Medrano, M., Pérez, P. F., and Abraham, A. G. (2008). Kefiran antagonizes cytopathic effects of Bacillus cereus extracellular factors. Int. J. Food Microbiol. 122, 1-7. doi: 10.1016/j.ijfoodmicro.2007.11.046
66. Metchnikoff, E. (1908). The Prolongation of Life. New York, NY: Putnam.
67. Miao, J., Guo, H., Ou, Y., Liu, G., Fang, X., Liao, Z., et al. (2014). Purification and characterization of bacteriocin F1, a novel bacteriocin produced by Lactobacillus paracasei subsp. tolerans FX-6 from Tibetan kefir, a traditional fermented milk from Tibet, China. Food Control 42, 48-53. doi: 10.1016/j.foodcont.2014.01.041
68. Miguel, M. G. D. C. P., Cardoso, P. G., de Assis Lago, L., and Schwan, R. F. (2010). Diversity of bacteria present in milk kefir grains using culture-dependent and culture-independent methods. Food Res. Int. 43, 1523-1528. doi: 10.1016/j.foodres.2010.04.031
69. Motaghi, M., Mazaheri, M., Moazami, N., Farkhondeh, A., Fooladi, M., and Goltapeh, E. (1997). Kefir production in Iran. World J. Microbiol. Biotechnol. 13, 579-581. doi: 10.1023/A:1018577728412
70. Murofushi, M., Mizuguchi, J., Aibara, K., and Matuhasi, T. (1986). Immunopotentiative effect of polysaccharide from kefir grain, KGF-C, administered orally in mice. Immunopharmacology 12, 29-35. doi: 10.1016/0162-3109(86)90049-4
71. Nalbantoglu, U., Cakar, A., Dogan, H., Abaci, N., Ustek, D., Sayood, K., et al. (2014). Metagenomic analysis of the microbial community in kefir grains. Food Microbiol. 41, 42-51. doi: 10.1016/j.fm.2014.01.014
72. Osada, K., Nagira, K., Teruya, K., Tachibana, H., Shirahata, S., and Murakami, H. (1993). Enhancement of interferon-beta production with sphingomyelin from fermented milk. Biotherapy 7, 115-123. doi: 10.1007/BF01877735
73. Parvez, S., Malik, K. A., Ah Kang, S., and Kim, H. Y. (2006). Probiotics and their fermented food products are beneficial for health. J. Appl. Microbiol. 100, 1171-1185. doi: 10.1111/j.1365-2672.2006.02963.x
74. Pintado, M. E., Da Silva, J. A. L., Fernandes, P. B., Malcata, F. X., and Hogg, T. A. (1996). Microbiological and rheological studies on Portuguese kefir grains. Int. J. Food Sci. Technol. 31, 15-26. doi: 10.1111/j.1365-2621.1996.16-316.x
75. Powell, J. E., Witthuhn, R. C., Todorov, S. D., and Dicks, L. M. T. (2007). Characterization of bacteriocin ST8KF produced by a kefir isolate Lactobacillus plantarum ST8KF. Int. Dairy J. 17, 190-198. doi: 10.1016/j.idairyj.2006.02.012
76. Quiros, A., Hernandez-Ledesma, B., Ramos, M., Amigo, L., and Recio, I. (2005). Angiotensin-converting enzyme inhibitory activity of peptides derived from caprine kefir. J. Dairy Sci 88, 3480-3487. doi: 10.3168/jds. S0022-0302(05)73032-0
77. Rahimzadeh, G., Seyedi Dolatabad, S., and Fallah Rostami, F. (2014). Comparison of two types of gels in improving burn wound. Crescent J. Med. Biol. Sci. 1, 28-32.
78. Rea, M., Lennartsson, T., Dillon, P., Drinan, F., Reville, W., Heapes, M., et al. (1996). Irish kefir-like grains: their structure, microbial composition and fermentation kinetics. J. Appl. Bacteriol. 81, 83-94. doi: 10.1111/j.1365-2672.1996.tb03286.x
79. Rea, M. C., Clayton, E., O'Connor, P. M., Shanahan, F., Kiely, B., Ross, R. P., et al. (2007). Antimicrobial activity of lacticin 3, 147 against clinical Clostridium difficile strains. J. Med. Microbiol. 56, 940-946. doi: 10.1099/jmm.0.47085-0
80. Rimada, P. S., and Abraham, A. G. (2006). Kefiran improves rheological properties of glucono-d-lactone induced skim milk gels. Int. Dairy J. 16, 33-39. doi: 10.1016/j.idairyj.2005.02.002
81. Rizk, S., Maalouf, K., and Baydoun, E. (2009). The antiproliferative effect of kefir cell-free fraction on HuT-102 malignant T lymphocytes. Clin. Lymphoma Myeloma 9(Suppl. 3), S198-S203. doi: 10.3816/CLM.2009.s.012
82. Rizk, S., Maalouf, K., Nasser, H., and El-Hayek, S. (2013). The Pro-apoptotic effect of kefir in Malignant T-lymphocytes Involves a p53 Dependent Pathway. Clin. Lymphoma Myeloma Leukemia 13(Suppl. 2), S367. doi: 10.1016/j.clml.2013.07.062
83. Rodrigues, K. L., Caputo, L. R., Carvalho, J. C., Evangelista, J., and Schneedorf, J. M. (2005). Antimicrobial and healing activity of kefir and kefiran extract. Int. J. Antimicrob. Agents 25, 404-408. doi: 10.1016/j.ijantimicag.2004.09.020
84. Romanin, D., Serradell, M., Gonzalez Maciel, D., Lausada, N., Garrote, G. L., and Rumbo, M. (2010). Down-regulation of intestinal epithelial innate response by probiotic yeasts isolated from kefir. Int. J. Food Microbiol. 140, 102-108. doi: 10.1016/j.ijfoodmicro.2010.04.014
85. Russell, S. L., Gold, M. J., Hartmann, M., Willing, B. P., Thorson, L., Wlodarska, M., et al. (2012). Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep. 13, 440-447. doi: 10.1038/embor.2012.32
86. Ryan, M. P., Rea, M. C., Hill, C., and Ross, R. P. (1996). An application in cheddar cheese manufacture for a strain of Lactococcus lactis producing a novel broad-spectrum bacteriocin, lacticin 3147. Appl. Environ. Microbiol. 62, 612-619.
87. Sakaguchi, S. (2011). Regulatory T cells: history and perspective. Methods Mol. Biol. 707, 3-17. doi: 10.1007/978-1-61737-979-6_1
88. Santos, A., San Mauro, M., Sanchez, A., Torres, J. M., and Marquina, D. (2003). The antimicrobial properties of different strains of Lactobacillus spp. isolated from kefir. Syst. Appl. Microbiol. 26, 434-437. doi: 10.1078/072320203322497464
89. Serafini, F., Turroni, F., Ruas-Madiedo, P., Lugli, G. A., Milani, C., Duranti, S., et al. (2014). Kefir fermented milk and kefiran promote growth of Bifidobacterium bifidum PRL2010 and modulate its gene expression. Int. J. Food Microbiol. 178, 50-59. doi: 10.1016/j.ijfoodmicro.2014.02.024
90. Sibel Akalin, A., Gönç, S., and Düzel, S. (1997). Influence of yogurt and acidophilus yogurt on serum cholesterol levels in mice. J. Dairy Sci. 80, 2721-2725. doi: 10.3168/jds. S0022-0302(97)76233-7
91. Simova, E., Beshkova, D., Angelov, A., Hristozova, T., Frengova, G., and Spasov, Z. (2002). Lactic acid bacteria and yeasts in kefir grains and kefir made from them. J. Ind. Microbiol. Biotechnol. 28, 1-6. doi: 10.1038/sj/jim/7000186
92. Sjogren, Y. M., Jenmalm, M. C., Bottcher, M. F., Bjorksten, B., and Sverremark-Ekstrom, E. (2009). Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clin. Exp. Allergy 39, 518-526. doi: 10.1111/j.1365-2222.2008.03156.x
93. Sorenson, C. M. (2004). Bcl-2 family members and disease. Biochim. Biophys. Acta 1644, 169-177. doi: 10.1016/j.bbamcr.2003.08.010
94. St-Onge, M. P., Farnworth, E. R., Savard, T., Chabot, D., Mafu, A., and Jones, P. J. (2002). Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810]. BMC Complement. Altern. Med. 2:1. doi: 10.1186/1472-6882-2-1
95. Takizawa, S., Kojima, S., Tamura, S., Fujinaga, S., Benno, Y., and Nakase, T. (1994). Lactobacillus kefirgranum sp. nov. and Lactobacillus parakefir sp. nov., two new species from kefir grains. Int. J. Syst. Evol. Microbiol. 44, 435-439.
96. Tamang, J. P., Holzapfel, W. H., and Watabane, K. (2016). Review: diversity of microorganisms in global fermented foods and beverages. Front. Microbiol. 7:377. doi: 10.3389/fmicb.2016.00377
97. Tamime, A. Y. (2002). Fermented milks: a historical food with modern applications-a review. Eur. J. Clin. Nutr. 56(Suppl. 4), S2-S15. doi: 10.1038/sj.ejcn.1601657
98. Tanabe, S. (2008). Analysis of food allergen structures and development of foods for allergic patients. Biosci. Biotechnol. Biochem. 72, 649-659. doi: 10.1271/bbb.70708
99. Tas, T. K., Ekinci, F. Y., and Guzel-Seydim, Z. B. (2012). Identification of microbial flora in kefir grains produced in Turkey using PCR. Int. J. Dairy Technol. 65, 126-131. doi: 10.1111/j.1471-0307.2011.00733.x
100. Thoreux, K., and Schmucker, D. L. (2001). Kefir milk enhances intestinal immunity in young but not old rats. J. Nutr. 131, 807-812.
101. Tsai, C.-C., Ke, P.-C., Hsu, T.-K., and Hsieh, Y.-M. (2012). Oral administration of multiple lactic acid bacteria strains suppressed allergic responses IgE in an ovalbumin-induced allergy BALB/c mouse model. Afr. J. Microbiol. Res. 6, 1206-1212.
102. Turroni, F., Serafini, F., Foroni, E., Duranti, S., Motherway, M. O. C., Taverniti, V., et al. (2013). Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions. Proc. Natl. Acad. Sci. U.S.A. 110, 11151-11156. doi: 10.1073/pnas.1303897110
103. Urdaneta, E., Barrenetxe, J., Aranguren, P., Irigoyen, A., Marzo, F., and Ibáñez, F. C. (2007). Intestinal beneficial effects of kefir-supplemented diet in rats. Nutr. Res. 27, 653-658. doi: 10.1016/j.nutres.2007.08.002
104. Vardjan, T., Lorbeg, P. M., Rogelj, I., and Majhenic, A. C. (2013). Characterization and stability of Lactobacilli and yeast microbiota in kefir grains. J. Dairy Sci. 96, 2729-2736. doi: 10.3168/jds.2012-5829
105. Villarruel, G., Rubio, D. M., Lopez, F., Cintioni, J., Gurevech, R., Romero, G., et al. (2007). Saccharomyces boulardii in acute childhood diarrhoea: a randomized, placebo-controlled study. Acta Paediatr. 96, 538-541. doi: 10.1111/j.1651-2227.2007.00191.x
106. Vinderola, C. G., Duarte, J., Thangavel, D., Perdigón, G., Farnworth, E., and Matar, C. (2005). Immunomodulating capacity of kefir. J. Dairy Res. 72, 195-202. doi: 10.1017/S0022029905000828
107. Vinderola, G., Perdigón, G., Duarte, J., Farnworth, E., and Matar, C. (2006a). Effects of the oral administration of the exopolysaccharide produced by Lactobacillus kefiranofaciens on the gut mucosal immunity. Cytokine 36, 254-260. doi: 10.1016/j.cyto.2007.01.003
108. Vinderola, G., Perdigon, G., Duarte, J., Thangavel, D., Farnworth, E., and Matar, C. (2006b). Effects of kefir fractions on innate immunity. Immunobiology 211, 149-156. doi: 10.1016/j.imbio.2005.08.005
109. Vujicic, I., Vulic, M., and Könyves, T. (1992). Assimilation of cholesterol in milk by kefir cultures. Biotechnol. Lett. 14, 847-850. doi: 10.1007/BF01029151
110. Wang, S.-Y., Chen, H.-C., Liu, J.-R., Lin, Y.-C., and Chen, M.-J. (2008). Identification of yeasts and evaluation of their distribution in Taiwanese kefir and viili starters. J. Dairy Sci. 91, 3798-3805. doi: 10.3168/jds.2007-0468
111. Wang, S.-Y., Chen, K.-N., Lo, Y.-M., Chiang, M.-L., Chen, H.-C., Liu, J.-R., et al. (2012). Investigation of microorganisms involved in biosynthesis of the kefir grain. Food Microbiol. 32, 274-285. doi: 10.1016/j.fm.2012.07.001
112. Wang, Y., Xu, N., Xi, A., Ahmed, Z., Zhang, B., and Bai, X. (2009). Effects of Lactobacillus plantarum MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high-cholesterol diet. Appl. Microbiol. Biotechnol. 84, 341-347. doi: 10.1007/s00253-009-2012-x
113. West, C. E. (2014). Gut microbiota and allergic disease: new findings. Curr. Opin. Clin. Nutr. Metab. Care 17, 261-266. doi: 10.1097/MCO.0000000000000044
114. WHO (1982). Prevention of coronary heart disease. World Health Organ. Tech. Rep. Ser. 678, 1-53.
115. Witthuhn, R., Schoeman, T., and Britz, T. (2005). Characterisation of the microbial population at different stages of Kefir production and Kefir grain mass cultivation. Int. Dairy J. 15, 383-389. doi: 10.1016/j.idairyj.2004.07.016
116. Witthuhn, R. C., Schoeman, T., and Britz, T. J. (2004). Isolation and characterization of the microbial population of different South African kefir grains. Int. J. Dairy Technol. 57, 33-37. doi: 10.1111/j.1471-0307.2004.00126.x
117. Wolever, T., Spadafora, P. J., Cunnane, S. C., and Pencharz, P. B. (1995). Propionate inhibits incorporation of colonic [1, 2-13C] acetate into plasma lipids in humans. Am. J. Clin. Nutr. 61, 1241-1247.
118. Wood, R. A. (2003). The natural history of food allergy. Pediatrics 111, 1631-1637.
119. Wszolek, M., Tamime, A., Muir, D., and Barclay, M. (2001). Properties of kefir made in Scotland and Poland using bovine, caprine and ovine milk with different starter cultures. LWT-Food Sci. Technol. 34, 251-261. doi: 10.1006/fstl.2001.0773
120. Xiao, J., Kondo, S., Takahashi, N., Miyaji, K., Oshida, K., Hiramatsu, A., et al. (2003). Effects of milk products fermented by Bifidobacterium longum on blood lipids in rats and healthy adult male volunteers. J. Dairy Sci. 86, 2452-2461. doi: 10.3168/jds. S0022-0302(03)73839-9
121. Xie, N., Zhou, T., and Li, B. (2012). Kefir yeasts enhance probiotic potentials of Lactobacillus paracasei H9: the positive effects of coaggregation between the two strains. Food Res. Int. 45, 394-401. doi: 10.1016/j.foodres.2011.10.045
122. Yazdanbakhsh, M., Kremsner, P. G., and van Ree, R. (2002). Allergy, parasites, and the hygiene hypothesis. Science 296, 490-494. doi: 10.1126/science.296.5567.490
123. Yoshida, Y., Yokoi, W., Ohishi, K., Ito, M., Naito, E., and Sawada, H. (2005). Effects of the cell wall of Kluyveromyces marxianus YIT 8292 on the plasma cholesterol and fecal sterol excretion in rats fed on a high-cholesterol diet. Biosci. Biotechnol. Biochem. 69, 714-723. doi: 10.1271/bbb.69.714
124. Yüksekdag, Z., Beyatli, Y., and Aslim, B. (2004). Determination of some characteristics coccoid forms of lactic acid bacteria isolated from Turkish kefirs with natural probiotic. J. WT-Food Sci. Technol. 37, 663-667. doi: 10.1016/j.lwt.2004.02.004
125. Zanirati, D. F., Abatemarco, M., de Cicco Sandes, S. H., Nicoli, J. R., Nunes, ÁC., and Neumann, E. (2015). Selection of lactic acid bacteria from Brazilian kefir grains for potential use as starter or probiotic cultures. Anaerobe 32, 70-76. doi: 10.1016/j.anaerobe.2014.12.007
126. Zheng, Y., Lu, Y., Wang, J., Yang, L., Pan, C., and Huang, Y. (2013). Probiotic properties of Lactobacillus strains isolated from Tibetan kefir grains. PLoS ONE 8:e69868. doi: 10.1371/journal.pone.0069868
127. Zhou, J., Liu, X., Jiang, H., and Dong, M. (2009). Analysis of the microflora in Tibetan kefir grains using denaturing gradient gel electrophoresis. Food Microbiol. 26, 770-775. doi: 10.1016/j.fm.2009.04.009
128. Zhuang, G., Liu, X.-M., Zhang, Q.-X., Tian, F.-W., Zhang, H., Zhang, H.-P., et al. (2012). Research advances with regards to clinical outcome and potential mechanisms of the cholesterol-lowering effects of probiotics. Clin. Lipidol. 7, 501-507. doi: 10.2217/clp.12.40