基于转录组学和蛋白质组学对益生菌Lactobacillus casei Zhang在牛乳和豆乳中生长机理的研究
|
摘要
Lactobacillus casei Zhang是从内蒙古地区传统发酵乳制品中分离到的一株具有优良益生性状的干酪乳杆菌,其对酸和胆盐具有较强的耐受性,同时具有抗菌、抗氧化和免疫调节等益生特性,是乳酸菌研究和益生菌开发利用的理想菌株。
以牛乳作为培养基来生产益生茵发酵乳制品得到了世界上研究者和市场的普遍认可。本研究结果显示,接种量(1×107CFU/mL)相同时,L. casei Zhang在豆乳中的生长速度显著快于牛乳(P<0.05),至发酵终点(pH4.5)所需时间J分别为14.5h和18h;发酵结束后,豆乳中活菌数可达109.10±0.08CFU/mL,显著高于牛乳中活菌数(108.24±0.09CFU/mL)(P<0.05).这一结果表明L. casei Zhang在豆乳中生长好于牛乳中,或许用豆乳作为基料生产益生菌发酵制品较牛乳更为合适。
为了探明L. casei Zhang在牛乳和豆乳中的生长机理,本研究依据其基因全序列,采用其基因组表达谱芯片和双向凝胶电泳、质谱技术,从基因转录组学和蛋白质组学水平对这一机理进行了研究。
转录组学分析表明,L. casei Zhang在牛乳中生长和发酵过程中,在稳定生长期(pH4.5)较对数生长期(pH5.2)共有84个基因显著表达,其中59个表达显著上调控基因中(P<0.05),40.5%与碳水化合物和能量代谢相关；而豆乳生长和发酵过程中,对数生长期(pH5.2)较迟滞生长期(pH6.4)有162基因表达显著不同(P<0.05),稳定生长期(pH4.5)较对数生长期(pH5.2)有63个基因表达显著不同(P<0.05),其中对数生长期48.6%的表达上调控基因(93个)与氨基酸的转运和代谢有关,稳定生长期48.8%的表达上调控(46个)与氨基酸转运和代谢相关。
蛋白质组学分析表明,L. casei Zhang在豆乳中生长,较牛乳共有144个差异表达蛋白点,其中迟滞生长期(pH6.4)34个,对数生长期(pH5.2)64个,稳定生长期(pH4.5)46个,三个时期表达上调控蛋白点分别为24个、34个和33个,编码这些表达上调控蛋白质的基因主要参与氨基酸和核苷酸的转运和代谢。
进一步分析表明,L. casei Zhang在牛乳生长过程中,主要上调控基因与PTC系统和磷酸戊糖途径PPP相关：而在豆乳生长过程中,主要上调控基因与蛋白水解酶系统(胞外蛋白酶PrtP、寡肽转运系统Opp和胞内肽酶Pep)、氨基酸(谷氨酸gιn、赖氨酸ιyS和甲硫氨酸met)和核苷酸(嘌呤Pur和嘧啶Pyr)代谢相关,尤其是蛋白水解酶系统的活跃表达,使得L. casei Zhang在豆乳能够分解大豆蛋白质为自身的生长提供充足氨基酸和核苷酸,这可能是其在豆乳中生长优于牛乳的主要原因。
本课题从基因水平上揭示L. casei Zhang在牛乳和豆乳中生长代谢机制,指出由于对牛乳和豆乳体系中蛋白质的水解和氨基酸的代谢不同,使其生长有所差异。
Lactobacillus casei Zhang is a well-recognized probiotic, which was isolated from traditional fermented milk products in Inner Mongolia area, it showed strong tolerance to acid and bile salt in vitro and antibacterial, antioixdantive and immune-regulatory effects in vivo, suggesting that it was an ideal strain for probiotic research.
Milk material is a kind of favorable carrier for probiotic, which has generally recognized by researchers and the market in the world. Results revealed that growing speed of L. casei Zhang was significantly higher in soy milk than bovine milk under the same inoculum (1×107CFU/mL). What is more, the fermentation time (to pH4.5) required was respectively14.5h and18h. At the end of fermentation, the living number of L. casei Zhang in soy milk (109.10±0.08CFU/mL) was Significantly higher than bovine milk (108.24±0.09CFU/mL), suggesting that growing of L. casei Zhang was better in soy milk than bovine milk. Perhaps, it is more suitable for soy milk to product probiotic fermented products than bovine milk.
According to complete genomic sequences of L. casei Zhang, growing mechanisms of L. casei Zhang in soy milk and bovine milk were analyzed from transcriptomics and proteomics through microarray biochip,2-dimensional gel electrophoresis and mass spectrum technique.
Result from transcriptomic analysis showed that the expressions of84genes in stationary phase (pH4.5) were significantly higher than these in exponential phase (pH5.2) during bovine milk fermentation. Among these, the expressions of59genes were significantly upregulated (P＜0.05) and40.5%of upregulated genes was associated with carbohydrate and energy metabolism.During soy milk fermentation, in comparison with exponential phase (pH5.2),162genes in lag phase (pH6.4) and63genes in stationary phase (pH4.5) were significantly expressed (P＜0.05). Furthermore,48.6%of upregulated genes (93genes) in exponential phase was associated with amino acid transport and metabolism while48.8%significantly regulated genes (46genes) in stationary phase was associated with amino acid transport and metabolism.
Result from proteomic analysis showed that a total of144protein spots were differently expressed including34spots in lag phase (pH6.4),64spots in exponential phase (pH5.2) and46spots in stationary phase (pH4.5) during growing of L. casei Zhang in soy milk compared to bovine milk. Furthermore,2-fold upregulated expression spots in three phases were respectively24,34and33. Most upregulated proteins related genes were associated with nucleotide and amino acids transport and metabolism.
Further analysis revealed that when L. casei Zhang is growing in bovine milk, the key upregulated genes were associated with PTC system and Pentose Phosphate Pathway; while in soy milk, associated with protein hydrolysis enzyme system (PrtP, Opp and Pep), amino acids (gln, lys and met) and nucleotide (Pur and Pyr), especilly the active expression of protein hydrolysis enzyme system. It makes that L. casei Zhang can decompose soybean protein and provide adequate amino acids and nucleotide for itself, which is the main explanation for well-growing L. casei Zhang in soy milk.
This study revealed the mechanisms of growing and metabolism of L. casei Zhang in bovine milk and soy milk at genetic level, and pointed out that growing differences were main due to different protein hydrolysis and amino acids metabolism within bovine and soy milk system.
以牛乳作为培养基来生产益生茵发酵乳制品得到了世界上研究者和市场的普遍认可。本研究结果显示,接种量(1×107CFU/mL)相同时,L. casei Zhang在豆乳中的生长速度显著快于牛乳(P<0.05),至发酵终点(pH4.5)所需时间J分别为14.5h和18h;发酵结束后,豆乳中活菌数可达109.10±0.08CFU/mL,显著高于牛乳中活菌数(108.24±0.09CFU/mL)(P<0.05).这一结果表明L. casei Zhang在豆乳中生长好于牛乳中,或许用豆乳作为基料生产益生菌发酵制品较牛乳更为合适。
为了探明L. casei Zhang在牛乳和豆乳中的生长机理,本研究依据其基因全序列,采用其基因组表达谱芯片和双向凝胶电泳、质谱技术,从基因转录组学和蛋白质组学水平对这一机理进行了研究。
转录组学分析表明,L. casei Zhang在牛乳中生长和发酵过程中,在稳定生长期(pH4.5)较对数生长期(pH5.2)共有84个基因显著表达,其中59个表达显著上调控基因中(P<0.05),40.5%与碳水化合物和能量代谢相关；而豆乳生长和发酵过程中,对数生长期(pH5.2)较迟滞生长期(pH6.4)有162基因表达显著不同(P<0.05),稳定生长期(pH4.5)较对数生长期(pH5.2)有63个基因表达显著不同(P<0.05),其中对数生长期48.6%的表达上调控基因(93个)与氨基酸的转运和代谢有关,稳定生长期48.8%的表达上调控(46个)与氨基酸转运和代谢相关。
蛋白质组学分析表明,L. casei Zhang在豆乳中生长,较牛乳共有144个差异表达蛋白点,其中迟滞生长期(pH6.4)34个,对数生长期(pH5.2)64个,稳定生长期(pH4.5)46个,三个时期表达上调控蛋白点分别为24个、34个和33个,编码这些表达上调控蛋白质的基因主要参与氨基酸和核苷酸的转运和代谢。
进一步分析表明,L. casei Zhang在牛乳生长过程中,主要上调控基因与PTC系统和磷酸戊糖途径PPP相关：而在豆乳生长过程中,主要上调控基因与蛋白水解酶系统(胞外蛋白酶PrtP、寡肽转运系统Opp和胞内肽酶Pep)、氨基酸(谷氨酸gιn、赖氨酸ιyS和甲硫氨酸met)和核苷酸(嘌呤Pur和嘧啶Pyr)代谢相关,尤其是蛋白水解酶系统的活跃表达,使得L. casei Zhang在豆乳能够分解大豆蛋白质为自身的生长提供充足氨基酸和核苷酸,这可能是其在豆乳中生长优于牛乳的主要原因。
本课题从基因水平上揭示L. casei Zhang在牛乳和豆乳中生长代谢机制,指出由于对牛乳和豆乳体系中蛋白质的水解和氨基酸的代谢不同,使其生长有所差异。
Lactobacillus casei Zhang is a well-recognized probiotic, which was isolated from traditional fermented milk products in Inner Mongolia area, it showed strong tolerance to acid and bile salt in vitro and antibacterial, antioixdantive and immune-regulatory effects in vivo, suggesting that it was an ideal strain for probiotic research.
Milk material is a kind of favorable carrier for probiotic, which has generally recognized by researchers and the market in the world. Results revealed that growing speed of L. casei Zhang was significantly higher in soy milk than bovine milk under the same inoculum (1×107CFU/mL). What is more, the fermentation time (to pH4.5) required was respectively14.5h and18h. At the end of fermentation, the living number of L. casei Zhang in soy milk (109.10±0.08CFU/mL) was Significantly higher than bovine milk (108.24±0.09CFU/mL), suggesting that growing of L. casei Zhang was better in soy milk than bovine milk. Perhaps, it is more suitable for soy milk to product probiotic fermented products than bovine milk.
According to complete genomic sequences of L. casei Zhang, growing mechanisms of L. casei Zhang in soy milk and bovine milk were analyzed from transcriptomics and proteomics through microarray biochip,2-dimensional gel electrophoresis and mass spectrum technique.
Result from transcriptomic analysis showed that the expressions of84genes in stationary phase (pH4.5) were significantly higher than these in exponential phase (pH5.2) during bovine milk fermentation. Among these, the expressions of59genes were significantly upregulated (P＜0.05) and40.5%of upregulated genes was associated with carbohydrate and energy metabolism.During soy milk fermentation, in comparison with exponential phase (pH5.2),162genes in lag phase (pH6.4) and63genes in stationary phase (pH4.5) were significantly expressed (P＜0.05). Furthermore,48.6%of upregulated genes (93genes) in exponential phase was associated with amino acid transport and metabolism while48.8%significantly regulated genes (46genes) in stationary phase was associated with amino acid transport and metabolism.
Result from proteomic analysis showed that a total of144protein spots were differently expressed including34spots in lag phase (pH6.4),64spots in exponential phase (pH5.2) and46spots in stationary phase (pH4.5) during growing of L. casei Zhang in soy milk compared to bovine milk. Furthermore,2-fold upregulated expression spots in three phases were respectively24,34and33. Most upregulated proteins related genes were associated with nucleotide and amino acids transport and metabolism.
Further analysis revealed that when L. casei Zhang is growing in bovine milk, the key upregulated genes were associated with PTC system and Pentose Phosphate Pathway; while in soy milk, associated with protein hydrolysis enzyme system (PrtP, Opp and Pep), amino acids (gln, lys and met) and nucleotide (Pur and Pyr), especilly the active expression of protein hydrolysis enzyme system. It makes that L. casei Zhang can decompose soybean protein and provide adequate amino acids and nucleotide for itself, which is the main explanation for well-growing L. casei Zhang in soy milk.
This study revealed the mechanisms of growing and metabolism of L. casei Zhang in bovine milk and soy milk at genetic level, and pointed out that growing differences were main due to different protein hydrolysis and amino acids metabolism within bovine and soy milk system.
引文
1 FAO/WHO. Guidelines for the evaluation of probiot ics in food. London, Ontario, Canada: Joint FAO/WHO Working Group, pp.2002,1-11
2 Marco M. L., Pavan S., Kleerebezem M. Towards understanding molecular modes of probiotic action [J]. Curr Opin Biotechnol,2006,17:204-210
3 Minocha A. Probiotics for preventive health [J]. Nutr Clin Pract,2009,24:227-241
4 Sherman P. M., Ossa J. C., Johnson-Henry K. Unraveling mechanisms of action of probiotics [J]. Nutr Clin Pract,2009,24:10-14
5 Round J. L., Mazmanian S. K.. The gut microbiota shapes intestinal immune responses during health and disease [J]. Nat Rev Immunol,2009,9:313-323
6 Ohashi Y., Ushida K. Health-benefi cial effects of probiotics:its mode of action [J]. Anim Sci J,2009,80:361-371
7 Ouwehand A. C., Salminen S., Isolauri E. Probiotics:an overview of beneficial effects [J]. Antonie van Leeuwenhoek,2002,82:279-289
8 Benno Y., He F., Hosoda M., Hashimoto H., Kojima T. U., Yamazaki K., Uno H., MykkSnen H., Salminen S. Effects of Lactobacillus GG yogurt on human intestinal microecology in Japanese subjects [J]. Nutr Today,1996,31:12S
9 Sui J., Leighton S., Busta F., Brady L.16S ribosomal DNA analysis of the faecal lactobacilli composition of human subjects consuming a probiotic strain Lactobacillus acidophilus NCFM [J]. J Appl Microbiol,2002,93:907-912
10 Marianelli C., Cifani N., Pasquali P. Evaluation of antimicrobial activity of probiotic bacteria against Salmonella enterica subsp. Enterica serovar typhimurium 1344 in a common medium under different environmental conditions [J]. Res Microbiol, 2010,161:673-680
11 Kim T. S., Hur J. W., Yu M. A., Cheigh C. I., Kim K. N., Hwang J. K., Pyun Y. R. Antagonism of Helicobacter pylori by bacteriocins of lactic acid bacteria [J]. J Food Prot, 2003,66:3-12
12 Gueimonde M., Margolles A., de los Reyes-Gavilan C. G., Salminen S. Competitive exclusion of enteropathogens from human intestinal mucus by Bifidobacterium strains with acquired resistance to bile a preliminary study [J]. Int J Food Microbiol,2007,113:228-232
13 Saxelin M., Tynkkynen S., Mattila-Sandholm T., de Vos W. M. Probiotic and other functional microbes:from markets to mechanisms [J]. Curr Opin Biotechnol,2005, 16:204-211
14 Resta-Lenert S., Barrett K. E. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC) [J]. Gut, 2003,52:988-997
15 Mack D. R., Ahrne S., Hyde L., Wei S., Holl ingsworth M. A. Extracel lular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro [J]. Gut,2003,52:827-833
16 Schlee M., Harder J., Koten B., Stange E. F., Wehkamp J., Fellermann K. Probiotic lactobacilli and VSL#3 induce enterocyte β-defensin 2 [J]. Clin Exp Immunol,2008, 151:528-535
17 Wehkamp J., Harder J., Wehkamp K., Wehkamp-von Meissner B., Schlee M., Enders C., Sonnenborn U., Nuding S., Bengmark S., Fellermann K., Schroder J. M., Stange E. F. NF-κ B- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coll Nissle 1917:a novel effect of a probiotic bacterium [J]. Infect Immun,2004,72:5750-5758
18 Johnson-Henry K. C., Donato K. A., Shen-Tu G., Gordanpour M., Sherman P. M. Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli 0157:H7-induced changes in epithelial barrier function [J]. Infect Immun,2008, 76:1340-1348
19 Montalto M., Maggiano N., Ricci R., Curigliano V., Santoro L., Di Nicuolo F., Vecchio F. M., Gasbarrini A., Gasbarrini G. Lactobacillus acidophilus protects tight junctions from aspirin damage in HT-29 cells [J]. Digestion,2004,69:225-228
20 Delcenserie V., Martel D., Lamoureux M., Amiot J., Boutin Y., Roy D. Immunomodulatory effects of probiotics in the intestinal tract [J]. Curr Issues Mol Biol,2008,10:37-54
21 Wells J.M. Immunomodulatory mechanisms of lactobacilli [J]. Microb Cell Fact,2011, 10 (Suppl 1):S17
22 Bezkorovainy A. Probiotics:determinants of survival and growth in the gut [J]. Am J Clin Nutr,2001,73:399S-405S
23 Fuller R. Probiotics in man and animals [J]. J Appl Bacteriol,1989,66:365-378
24 EFSA (European Food Safety Authority). Opinion of the Scientific Panel on Biological Hazards on the maintenance of the list of QPS microorganisms intentionally added to food or feed [J]. The EFSA Journal,2008,923:1-48
25 Saarela M., Mogensen G., Fonden R., Matto J., Mattila-Sandholm T. Probiotic bacteria: safety, functional and technological properties [J]. J Biotechnol,2000,84:197-215
26 Hickson M., D' Souza A. L., Muthu N., Rogers T. R., Want S., Rajkumar C., Bulpitt C. J. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics:randomised double blind placebo controlled trial [J]. BMJ,2007, 335:80
27 Weichselbaum E. Probiotics and health:a review of the evidence [J]. Nutr Bull,2009, 34:340-373
28 Sazawal S., Hiremath G., Dhingra U., Malik P., Deb S., Black R. E. Efficacy of probiotics in prevention of acute diarrhoea:a meta-analysis of masked, randomised, placebo-controlled trials [J]. Lancet Infect Dis,2006,6:374-382
29 Koebnick C., Wagner I., Leitzmann P., Stern U., Zunft H. J. F. Probiotic beverage containing Lactobacillus casei Shirota improves gastrointestinal symptoms in patients with chronic constipation [J]. Can J Gastroenterol,2003,17:655-659
30 Vesa T. H., Marteau P., Korpela R. Lactose intolerance [J]. J Am Coll Nutr,2000, 19:165S-175S
31 de Vrese M., Winkler P., Rautenberg P., Harder T., Noah C., Laue C., Ott S., Hampe J., Schreiber S., Heller K., Schrezenmeir J. Effect of Lactobacillus gasseriPA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes:a double blind, randomized, controlled trial [J]. Clin Nutr,2005,24:481-491
32 Minocha A. Probiotics for preventive health. Nutr Clin Pract,2009,24:227-241
33 Weizman Z., Asli G., Alsheikh A. Effect of a probiotic infant formula on infections in child care centers:Comparison of two probiotic agents [J]. Pediatrics,2005, 115:5-9
34 Giovannini M., Agostoni C., Riva E., Salvini F., Ruscitto A., Zuccotti G. V., Radaelli G. The Felicita Study Group. A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in preschool children with allergic asthma and/or rhinitis [J]. Pediatr Res,2007, 62:215-220
35 Ivory K., Chambers S. J., Pin C., Prieto E., Arqu e s J. L., Nicoletti C. Oral delivery of Lactobacillus casei Shirota modifi esallergeninduced immune responses in allergic rhinitis [J]. Clin Exp Allergy,2008,38:1282-1289
36 Mary Ellen Sanders. Overview of functional foods:emphasis on probiotic bacteria [J]. Int Diary Journal,1998,2:341-347
37 Aso Y., Akanzan H. Prophylactic effect of a Loctobacillus casei preparation the recurrence of superficial bladder cancer [J]. Urol Intl,1992,49:125-129
38 Whorwell P. J., Altringer L., Morel J., Bond Y., Charbonneau D.,O' Mahony L., Kiely B., Shanahan F., Quigley E. M. M. Efficacy of an encapsulated probiotic Bifidobacterium infant is 35624 in women with irritable bowel syndrome [J]. Am J Gastroenterol,2006,101:1581-1590
39 Marco M. L., Pavan S., Kleerebezem M. Towards understanding molecular modes of probiotic action [J]. Curr Opin Biotechnol,2006,17:204-210
40 Ohashi Y., Ushida K. Health-beneficial effects of probiotics:its mode of action [J]. Anim Sci J,2009,80:361-371
41 Saxelin M., Lassig A., Karjalainen H., Tynkkynen S., Surakka A., Vapaatalo H., Ja'rvenpaa S., Korpela R., Mutanen M., Hatakka K. Persistence of probiotic strains in the gastrointestinal tract when administered as capsules, yoghurt, or cheese [J]. Int J Food Microbiol,2010,144:293-300
42 Kurman J, A., Rasic J. L. The health potential of products containing bifidobacteria, in Therapeutic properties of fermented milk [M]. London:Elsevier Applied Food Science Series,1991, pp.1117-1581
43 Guo Z, Wang J, Yan L, Chen W, Liu X, Zhang H. In vitro comparation of probiotic properties of Lactobacillus casei Zhang, a potential new probiotic, with selected probiotic strains [J].Lwt-Food Sci Technol.2009,42:1640-1646
44云月英,王立平,陈永福,孟和毕力格,张和平.喂饲Lactobacillus casei Zhang对大鼠体内脂质代谢的影响[J].微生物学通报,2006,33(3)：60-64
45 Tuo Y, Zhang Q, Chu F, Merritt J, Menhe B, Sun T, Du R, Zhang H.Immunological evaluation of Lactobacillus casei Zhang:a newly isolated strain from koumiss in Inner Mongolia, China [J]. BMC Immunol,2008,9:68
46 张和平,张七斤,任贵强,包秋华.乳酸杆菌对攻毒小鼠的保护作用和对肠道菌群的影响[J].微生物学通报,2007,34(3)：447-451
47王俊国,孟和毕力格,张和平,陈永福,包秋华.干酪乳杆菌Zhang对大鼠抗氧化能力的影响[J].营养学报,2009,31(1)：63-65
48托娅,杜瑞亭,张和平.益生菌Lb. casei Zhang对H22荷瘤小鼠的抗肿瘤作用及机制[J].肿瘤防治研究,2010,37(4)：463-465
49 Zhang W, Yu D, Sun Z, Wu R, Chen X, Chen W, Meng H, Hu S, Zhang H. Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional home-made koumiss in Inner Mongolia of China[J]. J Bacteriol,2010, 192(19):5268-5269.
50 Wu R, Wang W, Yu D, Zhang W, Li Y, Sun Z, Wu J, Meng H, Zhang H. Proteomic analysis of Lactobacillus casei Zhang, a new probiotic bacterium isolated from traditionally home-made koumiss in Inner Mongolia of China [J]. Mol Cell Proteomics,2009,10: 2321-2338
51 Lee Y K, Nomoto K, Salminen S, et al. Handbook of Probiotics [M]. New York:John wiley & Sons Inc.1999
52 Okolie U. V., Ehiemere I.O. Use of soy bean products as cheap sources of protein in child-nutrition in Akpuoga Nike Community, in Enugu State South East, Nigeria [J]. Pakistan J Nutr,2009,8(4):491-494
53 Rajka B., Galja P., Sandy L. Influence of temperature and glucose addition on growth and survival of bacteria from BCT culture in soymilk [J]. Mljekarstvo,2008,58(2): 171-179
54 Wang Y. C., Yu R. C., Chou C. C. Growth and survival of Bifidobacteria and Lactic acid bacteria during the fermentation and storage of cultured soymilk drinks [J].Food Microbiol,2002,19 (5):501-508
55 Murti T. W., Lamberet G., Bouillanne C., Desmazeaud M. J., Landon M. Croissance des lactobacilles dans l'extrait de soja. Effets surla viscosit 6, les composes volatils et la proteolyse [J]. Sci des Aliments,1993,13:491-500
56 Kamaly K.M. Bifidobacteria fermentation of soybean milk [J]. Food Res Inter,1997, 30:675-682
57 Hou J. W., Yu R. C., Chou C. C. Changes in some components of soymilk during fermentation with bifidobacteria [J]. Food Res Inter,2000,33:393-397
58 Desai A., Small D., McGill A. E.J., Shah N. P. Metabolism of raffinose and stachyose in reconstituted skimmilk and of n-hexanal and pentanal in soymilk by bifidobacteria [J]. Biosci Microflora,2002,21:245-250
59 Shimakawa Y., Matsubara S., Yuki N., et al. Evaluation of Bifidobacterium breve strain Yakult-fermented soymilk as a probiotic food[J]. Inter J Food Microbiol,2003,81 (2): 131-136
60 Rossi E. A., Vendramini R. C., Carlos I. Z., Pei Y. C., de Valdez G. F. Development of a novel fermented soymilk product with potential probiotic properties[J].Eur Food Res Technol,1999,209(5):305-307
61 周集中,多罗西娅·汤普森,徐鹰,詹姆斯·蒂德耶.微生物功能基因组学[M].北京：化学工业出版社,2007,1
62 Kricka L. J. Microchips, microarrays, biochips and nanochips:personal laboratories for the 21st century [J]. Clin Chim Acta,2001,307 (1-2):219-223
63 Xie Y., Chou L. S, Cutler A., et al. DNA Macroarray profiling of Lactococcus lactis subsp. lactis IL1403 gene expression during environmental stresses [J]. Appl Environ Microbiol,2004,70(11):6738-6747
64 Lemieux B., Aharoni A., Schena M. Overview of DNA chI Ptechnology [J]. Mol Breeding, 1998,4:277-289
65 Kane M. D., Jatkoe T. A., Stump f.C.R., et al. Assessment of the sensitivity and specificity of oligonucleotide (50m er) m icroarrays [J]. Nucl Acids Res,2000,28: 4552-4557
66 Wang Q, W ang M, Kong F, et al. Development of a DNA microarray to identify the Streptococcus pneumonia eserotypes contained in the 23-valent pneumococcal polysaccharid evaccine and closely related serotypes [J]. J Microbiol Meth,2007, 68:128-136
67 Whitehead K., Versalovic J., Roos S., et al. Genomic and genetic characterization of the bile stress response of probiotic Lactobacillus reuteri ATCC 55730 [J]. Appl Environ Microbiol,2008,5:1812-1819
68 Parche S., Beleut M., Rezzonico E., Jacobs D., Arigoni F., Titgemeyer F., Jankovic I. Lactose-over-glucose preference in Bifidobacterium longum NCC2705:glcP, encoding a glucose transporter, is subject to lactose repression [J]. J Bacteriol, 2006,188:1260-1265
69 Klijn A., Mercenier A., Arigoni A. Lessons from the genomes of bifidobacteria [J]. FEMS Microbiol Rev,2005,29:491-509
70 Barrangou R., Azcarate-Peril M. A., Duong T., et al. Global analysis of carbohydrate utilization by Lactobacillus acidophilus using cDNA microarrays [J]. Proc Natl Acad Sci USA,2006,103(10):3816-3821
71 Azcarate-Peril M., A., McAuliffe 0., Altermann E., et al. Microarray analysis of a two-component regulatory system involved in acid resistance and proteolytic activity in Lactobacil lusacidophilus [J]. Appl Environ Microbiol,2005,71(10):5794-5804
72 Wilkins M., R., Sanchez J., C., Gooley A., A., Appel R., D., Humphery-Smith I., Hochstrasser D., F., Williams K., L. Progress with proteome projects:why all proteins expressed by a genome should be identified and how to do it [J]. Biotechnol Genet Eng Rev,1996,13:19-50
73贺福初.蛋白质组学研究——后基因组时代的生力军[J].科学通报,1999,44(2)：113-122
74 Siciliano R., A., Cacace G., Mazzeo M.,F., Morelli L., Elli M., Rossi M., Malorni A. Proteomic investigation of the aggregation phenomenon in Lactobacillus crispatus [J]. Biochim Biophys Acta,2008,1784(2):335-42
75 Champomier-Verges M. C., Maguin E., Mistou M.Y., Anglade P., Chich J.F. Lactic acid bacteria and proteomics:current knowledge and perspectives [J].J Chromatography, 2002,771:329
76 Anglade P., Demey E., Labas V., Le Caer J.P., Chich J. F. Towards a proteomic map of Lactococcus lactis NCDO 763[J]. Electrophoresis,2000,21:2546-2549.
77 Cohen D. P., Renes J., Bouwman F. C., Zoetendal E. C., Mariman E., de Vos W. M., Vaughan E. E. Proteomic analysis of log to stationary growth phase Lactobacillus plantarum cells and a 2-DE database [J]. Proteomics,2006,6:6485-6493
78 Lim E. M., Ehrlich D. S., Maguin E. Identification of stress-inducible proteins in Lactobacillus delbrueckii subsp. Bulgaricus [J]. Electrophoresis,2000,21: 2557-2561
79 Lorca G.L., de Valdez G. F. The effect of suboptimal growth temperature and growth phase on resistance of Lactobacillus acidophilus to environmental stress [J]. Cryobiology,1999,39:144-149
80 Yuan J, Zhu L, Liu X, et al. Proteome reference map and proteomic analysis of Bifidobacterium longum NCC2705 [J]. Mol Cell Proteomics,2006,5:1105-1118
81乌日娜.益生菌Lactobacillus casei Zhang蛋白质组学研究[M].博士学位论文,内蒙古农业大学,2009
82 Arena S., D' Ambrosio C., Renzone G., Rullo R., Ledda L., Vitale F., Maglione G., Varcamonti M., Ferrara L., Scaloni A. A study of Streptococcus thermophilus proteome by integrated analytical procedures and differential expression investigations [J]. Proteomics,2006,6:181-192
83 Carme Plumed-Ferrer, Kaisa M. Koistinen, Tiina L. Tolonen, Satu J. Lehesranta, Sirpa 0. Karenlampi, Elina Makimattila, Vesa Joutsjoki, Vesa Virtanen, and Atte von Wright. Comparative study of sugar fermentation and protein expression patterns of two Lactobacillus plantarum strains grown in three different media [J]. Appl Environ Microbiol,2008,74(17):5349-5358
84 Cohen D. P. A., Renes J., Bouwman F. G., Zoetendal E. G., Mariman E., de Vos W. M., Vaughan E. E. Proteomic analysis of log to stationary growth phase Lactobacillus plantarum cells and a 2-DE database [J]. Proteomics,2006,6(24):6485-6493
85 Kawarai T., Furukawa S., Ogihara H., Yamasaki M. Mixed-species biofilm formation by lactic acid bacteria and rice eine yeasts [J]. Appl Environ Microbiol,2007,73(14): 4673-4676
86 VanBogelen R. A., Neidhardt F. C., Cold shock induces a major ribosomal associated protein that unwinds double stranded RNA in Escherichia coli [J]. Proc Natl Acad Sci USA,1990,87:5589-5593
87 Ouwehand A. C., Salminen S., Isolauri E. Probiotics, an overview of beneficial effects [J]. Anton van Leeuw,2002,82:279-289
88 Vaughan E.E., de Vries M. C., Zoetendal E.G., et al. The intestinal LABs [J]. Anton Van Leeuw,2002,82:341-352
89 Canche-Pool E. B., Cortez-G 6 mez R., Flores-Mej i a R.,et al. Probiotics and autoimmunity:An evolutionary perspective [J]. Med Hypotheses,2007,70:657-660
90 Vitini E., Alvarez S., Medina M., et al. Gut mucosal immunostimulation by lactic acid bacteria [J]. Biocell,2000,24:223-232
91 Quattrucci E., Bruschi L., Manzi P., Aromolo R., Panfili G. Nutritional evaluation of typical and reformulated Italian cheeses [J]. J Sci Food Agr,1997,73:46-52
92 Zhang H, Xu J, Wang J, Menghebilige, Sun T, Li H, Guo M. A survey on chemical and microbiological composition of kurut, naturally fermented yak milk from Qinghai in China [J], Food Control,2008,19:578-586
93中华人民共和国国家标准[S].GB4789.35-2010.食品安全国家标准：食品微生物学检验.
94 Zhang W, Yu D, Sun Z, Wu R, Chen X, Chen W, Hu S, Meng H, Zhang H. Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional home-made koumiss in Inner Mongolia of China [J]. J Bacteriol,2010, 192:5268-5269
95 Tatusov R. L., Koonin E. V., Lipman D. J. A genomic perspective on protein families [J]. Science,1997,278:631-637
96 Livak K. J., Schmittgen T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 22DDCT method [S]. Methods,2001,25:402-408
97 Savijoki K., Ingmer H., Varmanen P. Proteolytic systems of lactic acid bacteria [J].Microbiol Biotechnol,2006,71:394-406
98 Juillard V., Laan H., Kunji E.R., Jeronimus-Stratingh C. M., Bruins A. P., Konings W. N. The extracellular PI-type proteinase of Lactococcus lactis hydrolyzes beta-casein into more than one hundred different oligopeptides [J]. J Bacteriol, 1995,177:3472-3478
99 Juillard V., Le Bars D., Kunji E.R., Konings W. N., Gripon J.C., Richard J. Oligopeptides are the main source of nitrogen for Lactococcus lactis during growth in milk [J]. Appl Environ Microbiol,1995,61:3024-3030
100 Tynkkynen S., Buist G., Kunji E., Kok J., Poolman B., Venema G., Haandrikman A. Genetic and biochemical characterization of the oligopeptide transport system of Lactococcus lactis [J]. J Bacteriol,1993,175:7523-7532
101 Gitton C., Meyrand M., Wang J., Caron C., Trubuil A., Guillot A., Mistou M. Y. Proteomic signature of Lactococcus lactis NCDO763 cultivated in milk [J]. App Env Microbiol,2005,71:7152-7163
102 Christensen J. E., Dudley E.G., Pederson J. A., Steele J. L. Peptidases and amino acid catabolism in lactic acid bacteria [J]. Ant Van Leeuw,1999,76:217-246
103 Derzelle S., Bolotin A., Mistou M. Y., Rul F. Proteome analysis of Streptococcus thermophilus grown in milk reveals pyruvate formate-lyase as the major upregulated protein [J]. Appl Environ Microbiol,2005,71 (12):8597-8605
104 den Hengst C.D., Groeneveld M., Kuipers O. P., Kok J. Identification and functional characterization of the Lactococcus lactis CodY-regulated branched-chain amino acid permease BcaP (CtrA) [J]. J Bacteriol,2006,188:3280-3289
105 Stucky K., Hagting A., Klein J.R., Matern H., Henrich B., Konings W. N., Plapp R. Cloning and characterization of brnQ, a gene encoding a low-affinity, branched-chain amino acid carrier in Lactobacillus delbruckii subsp. lactis DSM7290 [J]. Mol Gen Genet,1995,249:682-690
106 Matsubara K., Ohnishi K., Kiritani K. Nucleotide sequences and characterization of liv genes encoding components of the high-affinity branched-chain amino acid transport system in Salmonella typhimurium [J]. J Biochem,1992,112:93-101
107 Hebert E.M., De Giori G.S., Raya R. R. Isolation and characterization of a slowly milk-coagulating variant of Lactobacillus helveticus deficient in purine biosynthesis [J]. Appl Environ Microbiol,2001,67:1846-1850.
108 Dickely F., Nilsson D., Hansen E.B., Johansen E. solation of Lactococcus lactis nonsense suppressors and construction of a food-grade cloning vector [J]. Mol Microbiol,1995,15:839-847
109 BeyerN H., Roepstorff P., Hammer K., Kilstrup M. Proteome analysis of the purine stimulon from Lactococcus lactis [J]. Proteomics,2003,3(5):786-797
110 Gitton C., Meyrand M., Wang J. H., Caron C., Trubuil A., Guillot A., Mistou M. Y. Proteomic signature of Lactococcus lactis NCD0763 cultivated in milk [J]. Appl Environ Microbiol,2005,71(11):7152-7163
111 Beyer N. H., Roepstorff P., Hammer K., Kilstrup M. Proteome analysis of the purine stimulon from Lactococcus lactis [J]. Proteomics,2003,3:786-797
112 Herve-Jimenez L., Guillouard I., Guedon E., Boudebbouze S., et al. Postgenomic analysis of streptococcus thermophilus cocultivated in milk with Lactobacillus delbrueckii subsp. bulgaricus:involvement of nitrogen, purine, and iron metabolism. Appl Environ Microbiol,2009,75:2062-2073
113 Gitton C., Meyrand M., Wang J., Caron C., et al. Proteomic signature of Lactococcus lactls NCDO763 cultivated in milk [J]. Appl Environ Microbiol,2005,71:7152-7163
114 Postma P. W., Lengeler J. W., and Jacobson G. R. Phosphoenol-pyruvate:carbohydrate phosphotransferase systems of bacteria [J]. Microbiol Rev,1993,57:543-94
115 Simoni R. D., Levinthal M., Kundig F. D., Kundig W., Anderson B., Hartman P. E., Roseman S. Genetic evidence for the role of a bacterial phosphotransferase system in sugar transport [J]. Proc Natl Acad Sci U S A,1967,58:1963-1970
116 Reizer J., Saier M. H. Jr. Modular multidoma in phosphoryltransfer proteins of bacteria [J]. Curr Opin Struct Biol,1997,7:407-415
117 Saier M. H. Jr. Protein phosphorylation and allosteric control of inducer exclusion and catabolite repression by the bacterial phosphoenol-pyruvate:sugar phosphotransferase system [J]. Microbiol Rev,1989,53:109-120
118 Saier M. H. Jr., Reizer J. The bacterial phosphotransferase system:new frontiers 30 years later [J]. Mol Microbiol,1994,13:755-764
119 Lengeler J.W., Jahreis K. Phosphotransferase systems or PTSs as carbohydrate transport and as signal transduction systems [J]. Handbook of biological physics, 1996,2:573-598
120 Cohen D. P., Renes J., Bouwman F. G., Zoetendal E. G., Mariman E., de Vos W. M., Vaughan E. E. Proteomic analysis of log to stationary growth phase Lactobacillus plantarum cells and a 2-DE database [J]. Proteomics,2006,6:6485-6493
121 Herve-Jimenez L., Guillouard I., Guedon E., Gautier C., Boudebbouze S., Hols P., Monnet V., Rul F., Maguin E. Physiology of Streptococcus thermophilus during the late stage of milk fermentation with special regard to sulfur amino-acid metabolism [J]. Proteomics,2008,8:4273-4286
122 Gao H, Jiang X, Pogliano K, Aronson A. The Elbeta and E2 subunits of the Bacillus subtilis pyruvate dehydrogenase complex are involved in regulation of sporulation [J]. J Bacteriol,2002,184:2780-2788
123 McLeod A., Zagorec M., Champomier-Verges M. C., Naterstad K., Axelsson L. Primary metabolism in Lactobacillus sakei food isolates by proteomic analysis [J]. BMC Microbiol,2006,10:120
124 Duche O., Tremoulet F., Glaser P., Labadie J. Salt stress proteins induced in Listeria monocytogenes [J]. App Env Microbiol,2002,68:1491-1498
125 Salotra P., Singh D. K., Seal K.P., Krishna N., Jaffe H., Bhatnagar R. Expression of DnaK and GroEL homologs in Leuconostoc esenteroides in response to heat shock, cold shock or chemical stress [J]. FEMS Microbiol Lett,1995,131:57-62
126 Larsen N., Boye M., Siegumfeldt H., Jakobsen M. Differential expression of proteins and genes in the lag phase of Lactococcus lactis subsp. lactis grown in synthetic medium and reconstituted skim milk [J]. Appl Env Microbiol,2006,72:1173-1179
127 Martin M. G., Sender P. D., Peiru S., de Mendoza D., Magni C. Acid-inducible transcription of the operon encoding the citrate lyase complex of Lactococcus lactis Biovar diacetylactis CRL264 [J]. J Bacteriol,2004,186:5649-5660
128 Stulke J., Arnaud M., Rapoport G., Martin-Verstraete I. PRD—a protein domain involved in PTS-dependent induction and carbon catabolite repression of catabolic operons in bacteria [J]. Mol Microbiol,1998,28:865-874
129 Saulnier D. M., Molenaar D., de Vos W. M., Gibson G. R., Kolida S. Identification of prebiotic fructooligosaccharide metabolism in Lactobacillus plantarum WCFS1 through microarrays [J]. Appl Environ Microbiol,2007,73:1753-1765
130 Redon E., Loubiere P., Cocaign-Bousquet M. Transcriptome analysis of the progressive adaptation of Lactococcus lactis to carbon starvation [J]. J Bacteriol,2005,187: 3589-3592
131 Sheng J., Marquis R.E.Malolactic fermentation by Streptococcus mutans [J]. FEMS Microbiol Lett,2007,272:196-201
132 Frees D., Savijoki K., Varmanen P., Ingmer H. Clp ATPases and ClpP proteolytic complexes regulate vital biological processes in low GC, Grampositive bacteria[J]. Mol Microbiol,2007,63:1285-1295
133 Lim E. M., Smokvina T., Chervaux C., Ehrlich S. D., Maguin E. Seventh symposium on lactic acid bacteria. Genetics, Metabolism and Applications [J]. FEMS,2002, p85
134 Chan E., Weiss B. Endonuclease Ⅳ of Escherichia coli is induced by paraquat [J]. Proc Natl Acad Sci U S A,1987,84:3189-3193
2 Marco M. L., Pavan S., Kleerebezem M. Towards understanding molecular modes of probiotic action [J]. Curr Opin Biotechnol,2006,17:204-210
3 Minocha A. Probiotics for preventive health [J]. Nutr Clin Pract,2009,24:227-241
4 Sherman P. M., Ossa J. C., Johnson-Henry K. Unraveling mechanisms of action of probiotics [J]. Nutr Clin Pract,2009,24:10-14
5 Round J. L., Mazmanian S. K.. The gut microbiota shapes intestinal immune responses during health and disease [J]. Nat Rev Immunol,2009,9:313-323
6 Ohashi Y., Ushida K. Health-benefi cial effects of probiotics:its mode of action [J]. Anim Sci J,2009,80:361-371
7 Ouwehand A. C., Salminen S., Isolauri E. Probiotics:an overview of beneficial effects [J]. Antonie van Leeuwenhoek,2002,82:279-289
8 Benno Y., He F., Hosoda M., Hashimoto H., Kojima T. U., Yamazaki K., Uno H., MykkSnen H., Salminen S. Effects of Lactobacillus GG yogurt on human intestinal microecology in Japanese subjects [J]. Nutr Today,1996,31:12S
9 Sui J., Leighton S., Busta F., Brady L.16S ribosomal DNA analysis of the faecal lactobacilli composition of human subjects consuming a probiotic strain Lactobacillus acidophilus NCFM [J]. J Appl Microbiol,2002,93:907-912
10 Marianelli C., Cifani N., Pasquali P. Evaluation of antimicrobial activity of probiotic bacteria against Salmonella enterica subsp. Enterica serovar typhimurium 1344 in a common medium under different environmental conditions [J]. Res Microbiol, 2010,161:673-680
11 Kim T. S., Hur J. W., Yu M. A., Cheigh C. I., Kim K. N., Hwang J. K., Pyun Y. R. Antagonism of Helicobacter pylori by bacteriocins of lactic acid bacteria [J]. J Food Prot, 2003,66:3-12
12 Gueimonde M., Margolles A., de los Reyes-Gavilan C. G., Salminen S. Competitive exclusion of enteropathogens from human intestinal mucus by Bifidobacterium strains with acquired resistance to bile a preliminary study [J]. Int J Food Microbiol,2007,113:228-232
13 Saxelin M., Tynkkynen S., Mattila-Sandholm T., de Vos W. M. Probiotic and other functional microbes:from markets to mechanisms [J]. Curr Opin Biotechnol,2005, 16:204-211
14 Resta-Lenert S., Barrett K. E. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC) [J]. Gut, 2003,52:988-997
15 Mack D. R., Ahrne S., Hyde L., Wei S., Holl ingsworth M. A. Extracel lular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro [J]. Gut,2003,52:827-833
16 Schlee M., Harder J., Koten B., Stange E. F., Wehkamp J., Fellermann K. Probiotic lactobacilli and VSL#3 induce enterocyte β-defensin 2 [J]. Clin Exp Immunol,2008, 151:528-535
17 Wehkamp J., Harder J., Wehkamp K., Wehkamp-von Meissner B., Schlee M., Enders C., Sonnenborn U., Nuding S., Bengmark S., Fellermann K., Schroder J. M., Stange E. F. NF-κ B- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coll Nissle 1917:a novel effect of a probiotic bacterium [J]. Infect Immun,2004,72:5750-5758
18 Johnson-Henry K. C., Donato K. A., Shen-Tu G., Gordanpour M., Sherman P. M. Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli 0157:H7-induced changes in epithelial barrier function [J]. Infect Immun,2008, 76:1340-1348
19 Montalto M., Maggiano N., Ricci R., Curigliano V., Santoro L., Di Nicuolo F., Vecchio F. M., Gasbarrini A., Gasbarrini G. Lactobacillus acidophilus protects tight junctions from aspirin damage in HT-29 cells [J]. Digestion,2004,69:225-228
20 Delcenserie V., Martel D., Lamoureux M., Amiot J., Boutin Y., Roy D. Immunomodulatory effects of probiotics in the intestinal tract [J]. Curr Issues Mol Biol,2008,10:37-54
21 Wells J.M. Immunomodulatory mechanisms of lactobacilli [J]. Microb Cell Fact,2011, 10 (Suppl 1):S17
22 Bezkorovainy A. Probiotics:determinants of survival and growth in the gut [J]. Am J Clin Nutr,2001,73:399S-405S
23 Fuller R. Probiotics in man and animals [J]. J Appl Bacteriol,1989,66:365-378
24 EFSA (European Food Safety Authority). Opinion of the Scientific Panel on Biological Hazards on the maintenance of the list of QPS microorganisms intentionally added to food or feed [J]. The EFSA Journal,2008,923:1-48
25 Saarela M., Mogensen G., Fonden R., Matto J., Mattila-Sandholm T. Probiotic bacteria: safety, functional and technological properties [J]. J Biotechnol,2000,84:197-215
26 Hickson M., D' Souza A. L., Muthu N., Rogers T. R., Want S., Rajkumar C., Bulpitt C. J. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics:randomised double blind placebo controlled trial [J]. BMJ,2007, 335:80
27 Weichselbaum E. Probiotics and health:a review of the evidence [J]. Nutr Bull,2009, 34:340-373
28 Sazawal S., Hiremath G., Dhingra U., Malik P., Deb S., Black R. E. Efficacy of probiotics in prevention of acute diarrhoea:a meta-analysis of masked, randomised, placebo-controlled trials [J]. Lancet Infect Dis,2006,6:374-382
29 Koebnick C., Wagner I., Leitzmann P., Stern U., Zunft H. J. F. Probiotic beverage containing Lactobacillus casei Shirota improves gastrointestinal symptoms in patients with chronic constipation [J]. Can J Gastroenterol,2003,17:655-659
30 Vesa T. H., Marteau P., Korpela R. Lactose intolerance [J]. J Am Coll Nutr,2000, 19:165S-175S
31 de Vrese M., Winkler P., Rautenberg P., Harder T., Noah C., Laue C., Ott S., Hampe J., Schreiber S., Heller K., Schrezenmeir J. Effect of Lactobacillus gasseriPA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes:a double blind, randomized, controlled trial [J]. Clin Nutr,2005,24:481-491
32 Minocha A. Probiotics for preventive health. Nutr Clin Pract,2009,24:227-241
33 Weizman Z., Asli G., Alsheikh A. Effect of a probiotic infant formula on infections in child care centers:Comparison of two probiotic agents [J]. Pediatrics,2005, 115:5-9
34 Giovannini M., Agostoni C., Riva E., Salvini F., Ruscitto A., Zuccotti G. V., Radaelli G. The Felicita Study Group. A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in preschool children with allergic asthma and/or rhinitis [J]. Pediatr Res,2007, 62:215-220
35 Ivory K., Chambers S. J., Pin C., Prieto E., Arqu e s J. L., Nicoletti C. Oral delivery of Lactobacillus casei Shirota modifi esallergeninduced immune responses in allergic rhinitis [J]. Clin Exp Allergy,2008,38:1282-1289
36 Mary Ellen Sanders. Overview of functional foods:emphasis on probiotic bacteria [J]. Int Diary Journal,1998,2:341-347
37 Aso Y., Akanzan H. Prophylactic effect of a Loctobacillus casei preparation the recurrence of superficial bladder cancer [J]. Urol Intl,1992,49:125-129
38 Whorwell P. J., Altringer L., Morel J., Bond Y., Charbonneau D.,O' Mahony L., Kiely B., Shanahan F., Quigley E. M. M. Efficacy of an encapsulated probiotic Bifidobacterium infant is 35624 in women with irritable bowel syndrome [J]. Am J Gastroenterol,2006,101:1581-1590
39 Marco M. L., Pavan S., Kleerebezem M. Towards understanding molecular modes of probiotic action [J]. Curr Opin Biotechnol,2006,17:204-210
40 Ohashi Y., Ushida K. Health-beneficial effects of probiotics:its mode of action [J]. Anim Sci J,2009,80:361-371
41 Saxelin M., Lassig A., Karjalainen H., Tynkkynen S., Surakka A., Vapaatalo H., Ja'rvenpaa S., Korpela R., Mutanen M., Hatakka K. Persistence of probiotic strains in the gastrointestinal tract when administered as capsules, yoghurt, or cheese [J]. Int J Food Microbiol,2010,144:293-300
42 Kurman J, A., Rasic J. L. The health potential of products containing bifidobacteria, in Therapeutic properties of fermented milk [M]. London:Elsevier Applied Food Science Series,1991, pp.1117-1581
43 Guo Z, Wang J, Yan L, Chen W, Liu X, Zhang H. In vitro comparation of probiotic properties of Lactobacillus casei Zhang, a potential new probiotic, with selected probiotic strains [J].Lwt-Food Sci Technol.2009,42:1640-1646
44云月英,王立平,陈永福,孟和毕力格,张和平.喂饲Lactobacillus casei Zhang对大鼠体内脂质代谢的影响[J].微生物学通报,2006,33(3)：60-64
45 Tuo Y, Zhang Q, Chu F, Merritt J, Menhe B, Sun T, Du R, Zhang H.Immunological evaluation of Lactobacillus casei Zhang:a newly isolated strain from koumiss in Inner Mongolia, China [J]. BMC Immunol,2008,9:68
46 张和平,张七斤,任贵强,包秋华.乳酸杆菌对攻毒小鼠的保护作用和对肠道菌群的影响[J].微生物学通报,2007,34(3)：447-451
47王俊国,孟和毕力格,张和平,陈永福,包秋华.干酪乳杆菌Zhang对大鼠抗氧化能力的影响[J].营养学报,2009,31(1)：63-65
48托娅,杜瑞亭,张和平.益生菌Lb. casei Zhang对H22荷瘤小鼠的抗肿瘤作用及机制[J].肿瘤防治研究,2010,37(4)：463-465
49 Zhang W, Yu D, Sun Z, Wu R, Chen X, Chen W, Meng H, Hu S, Zhang H. Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional home-made koumiss in Inner Mongolia of China[J]. J Bacteriol,2010, 192(19):5268-5269.
50 Wu R, Wang W, Yu D, Zhang W, Li Y, Sun Z, Wu J, Meng H, Zhang H. Proteomic analysis of Lactobacillus casei Zhang, a new probiotic bacterium isolated from traditionally home-made koumiss in Inner Mongolia of China [J]. Mol Cell Proteomics,2009,10: 2321-2338
51 Lee Y K, Nomoto K, Salminen S, et al. Handbook of Probiotics [M]. New York:John wiley & Sons Inc.1999
52 Okolie U. V., Ehiemere I.O. Use of soy bean products as cheap sources of protein in child-nutrition in Akpuoga Nike Community, in Enugu State South East, Nigeria [J]. Pakistan J Nutr,2009,8(4):491-494
53 Rajka B., Galja P., Sandy L. Influence of temperature and glucose addition on growth and survival of bacteria from BCT culture in soymilk [J]. Mljekarstvo,2008,58(2): 171-179
54 Wang Y. C., Yu R. C., Chou C. C. Growth and survival of Bifidobacteria and Lactic acid bacteria during the fermentation and storage of cultured soymilk drinks [J].Food Microbiol,2002,19 (5):501-508
55 Murti T. W., Lamberet G., Bouillanne C., Desmazeaud M. J., Landon M. Croissance des lactobacilles dans l'extrait de soja. Effets surla viscosit 6, les composes volatils et la proteolyse [J]. Sci des Aliments,1993,13:491-500
56 Kamaly K.M. Bifidobacteria fermentation of soybean milk [J]. Food Res Inter,1997, 30:675-682
57 Hou J. W., Yu R. C., Chou C. C. Changes in some components of soymilk during fermentation with bifidobacteria [J]. Food Res Inter,2000,33:393-397
58 Desai A., Small D., McGill A. E.J., Shah N. P. Metabolism of raffinose and stachyose in reconstituted skimmilk and of n-hexanal and pentanal in soymilk by bifidobacteria [J]. Biosci Microflora,2002,21:245-250
59 Shimakawa Y., Matsubara S., Yuki N., et al. Evaluation of Bifidobacterium breve strain Yakult-fermented soymilk as a probiotic food[J]. Inter J Food Microbiol,2003,81 (2): 131-136
60 Rossi E. A., Vendramini R. C., Carlos I. Z., Pei Y. C., de Valdez G. F. Development of a novel fermented soymilk product with potential probiotic properties[J].Eur Food Res Technol,1999,209(5):305-307
61 周集中,多罗西娅·汤普森,徐鹰,詹姆斯·蒂德耶.微生物功能基因组学[M].北京：化学工业出版社,2007,1
62 Kricka L. J. Microchips, microarrays, biochips and nanochips:personal laboratories for the 21st century [J]. Clin Chim Acta,2001,307 (1-2):219-223
63 Xie Y., Chou L. S, Cutler A., et al. DNA Macroarray profiling of Lactococcus lactis subsp. lactis IL1403 gene expression during environmental stresses [J]. Appl Environ Microbiol,2004,70(11):6738-6747
64 Lemieux B., Aharoni A., Schena M. Overview of DNA chI Ptechnology [J]. Mol Breeding, 1998,4:277-289
65 Kane M. D., Jatkoe T. A., Stump f.C.R., et al. Assessment of the sensitivity and specificity of oligonucleotide (50m er) m icroarrays [J]. Nucl Acids Res,2000,28: 4552-4557
66 Wang Q, W ang M, Kong F, et al. Development of a DNA microarray to identify the Streptococcus pneumonia eserotypes contained in the 23-valent pneumococcal polysaccharid evaccine and closely related serotypes [J]. J Microbiol Meth,2007, 68:128-136
67 Whitehead K., Versalovic J., Roos S., et al. Genomic and genetic characterization of the bile stress response of probiotic Lactobacillus reuteri ATCC 55730 [J]. Appl Environ Microbiol,2008,5:1812-1819
68 Parche S., Beleut M., Rezzonico E., Jacobs D., Arigoni F., Titgemeyer F., Jankovic I. Lactose-over-glucose preference in Bifidobacterium longum NCC2705:glcP, encoding a glucose transporter, is subject to lactose repression [J]. J Bacteriol, 2006,188:1260-1265
69 Klijn A., Mercenier A., Arigoni A. Lessons from the genomes of bifidobacteria [J]. FEMS Microbiol Rev,2005,29:491-509
70 Barrangou R., Azcarate-Peril M. A., Duong T., et al. Global analysis of carbohydrate utilization by Lactobacillus acidophilus using cDNA microarrays [J]. Proc Natl Acad Sci USA,2006,103(10):3816-3821
71 Azcarate-Peril M., A., McAuliffe 0., Altermann E., et al. Microarray analysis of a two-component regulatory system involved in acid resistance and proteolytic activity in Lactobacil lusacidophilus [J]. Appl Environ Microbiol,2005,71(10):5794-5804
72 Wilkins M., R., Sanchez J., C., Gooley A., A., Appel R., D., Humphery-Smith I., Hochstrasser D., F., Williams K., L. Progress with proteome projects:why all proteins expressed by a genome should be identified and how to do it [J]. Biotechnol Genet Eng Rev,1996,13:19-50
73贺福初.蛋白质组学研究——后基因组时代的生力军[J].科学通报,1999,44(2)：113-122
74 Siciliano R., A., Cacace G., Mazzeo M.,F., Morelli L., Elli M., Rossi M., Malorni A. Proteomic investigation of the aggregation phenomenon in Lactobacillus crispatus [J]. Biochim Biophys Acta,2008,1784(2):335-42
75 Champomier-Verges M. C., Maguin E., Mistou M.Y., Anglade P., Chich J.F. Lactic acid bacteria and proteomics:current knowledge and perspectives [J].J Chromatography, 2002,771:329
76 Anglade P., Demey E., Labas V., Le Caer J.P., Chich J. F. Towards a proteomic map of Lactococcus lactis NCDO 763[J]. Electrophoresis,2000,21:2546-2549.
77 Cohen D. P., Renes J., Bouwman F. C., Zoetendal E. C., Mariman E., de Vos W. M., Vaughan E. E. Proteomic analysis of log to stationary growth phase Lactobacillus plantarum cells and a 2-DE database [J]. Proteomics,2006,6:6485-6493
78 Lim E. M., Ehrlich D. S., Maguin E. Identification of stress-inducible proteins in Lactobacillus delbrueckii subsp. Bulgaricus [J]. Electrophoresis,2000,21: 2557-2561
79 Lorca G.L., de Valdez G. F. The effect of suboptimal growth temperature and growth phase on resistance of Lactobacillus acidophilus to environmental stress [J]. Cryobiology,1999,39:144-149
80 Yuan J, Zhu L, Liu X, et al. Proteome reference map and proteomic analysis of Bifidobacterium longum NCC2705 [J]. Mol Cell Proteomics,2006,5:1105-1118
81乌日娜.益生菌Lactobacillus casei Zhang蛋白质组学研究[M].博士学位论文,内蒙古农业大学,2009
82 Arena S., D' Ambrosio C., Renzone G., Rullo R., Ledda L., Vitale F., Maglione G., Varcamonti M., Ferrara L., Scaloni A. A study of Streptococcus thermophilus proteome by integrated analytical procedures and differential expression investigations [J]. Proteomics,2006,6:181-192
83 Carme Plumed-Ferrer, Kaisa M. Koistinen, Tiina L. Tolonen, Satu J. Lehesranta, Sirpa 0. Karenlampi, Elina Makimattila, Vesa Joutsjoki, Vesa Virtanen, and Atte von Wright. Comparative study of sugar fermentation and protein expression patterns of two Lactobacillus plantarum strains grown in three different media [J]. Appl Environ Microbiol,2008,74(17):5349-5358
84 Cohen D. P. A., Renes J., Bouwman F. G., Zoetendal E. G., Mariman E., de Vos W. M., Vaughan E. E. Proteomic analysis of log to stationary growth phase Lactobacillus plantarum cells and a 2-DE database [J]. Proteomics,2006,6(24):6485-6493
85 Kawarai T., Furukawa S., Ogihara H., Yamasaki M. Mixed-species biofilm formation by lactic acid bacteria and rice eine yeasts [J]. Appl Environ Microbiol,2007,73(14): 4673-4676
86 VanBogelen R. A., Neidhardt F. C., Cold shock induces a major ribosomal associated protein that unwinds double stranded RNA in Escherichia coli [J]. Proc Natl Acad Sci USA,1990,87:5589-5593
87 Ouwehand A. C., Salminen S., Isolauri E. Probiotics, an overview of beneficial effects [J]. Anton van Leeuw,2002,82:279-289
88 Vaughan E.E., de Vries M. C., Zoetendal E.G., et al. The intestinal LABs [J]. Anton Van Leeuw,2002,82:341-352
89 Canche-Pool E. B., Cortez-G 6 mez R., Flores-Mej i a R.,et al. Probiotics and autoimmunity:An evolutionary perspective [J]. Med Hypotheses,2007,70:657-660
90 Vitini E., Alvarez S., Medina M., et al. Gut mucosal immunostimulation by lactic acid bacteria [J]. Biocell,2000,24:223-232
91 Quattrucci E., Bruschi L., Manzi P., Aromolo R., Panfili G. Nutritional evaluation of typical and reformulated Italian cheeses [J]. J Sci Food Agr,1997,73:46-52
92 Zhang H, Xu J, Wang J, Menghebilige, Sun T, Li H, Guo M. A survey on chemical and microbiological composition of kurut, naturally fermented yak milk from Qinghai in China [J], Food Control,2008,19:578-586
93中华人民共和国国家标准[S].GB4789.35-2010.食品安全国家标准：食品微生物学检验.
94 Zhang W, Yu D, Sun Z, Wu R, Chen X, Chen W, Hu S, Meng H, Zhang H. Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional home-made koumiss in Inner Mongolia of China [J]. J Bacteriol,2010, 192:5268-5269
95 Tatusov R. L., Koonin E. V., Lipman D. J. A genomic perspective on protein families [J]. Science,1997,278:631-637
96 Livak K. J., Schmittgen T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 22DDCT method [S]. Methods,2001,25:402-408
97 Savijoki K., Ingmer H., Varmanen P. Proteolytic systems of lactic acid bacteria [J].Microbiol Biotechnol,2006,71:394-406
98 Juillard V., Laan H., Kunji E.R., Jeronimus-Stratingh C. M., Bruins A. P., Konings W. N. The extracellular PI-type proteinase of Lactococcus lactis hydrolyzes beta-casein into more than one hundred different oligopeptides [J]. J Bacteriol, 1995,177:3472-3478
99 Juillard V., Le Bars D., Kunji E.R., Konings W. N., Gripon J.C., Richard J. Oligopeptides are the main source of nitrogen for Lactococcus lactis during growth in milk [J]. Appl Environ Microbiol,1995,61:3024-3030
100 Tynkkynen S., Buist G., Kunji E., Kok J., Poolman B., Venema G., Haandrikman A. Genetic and biochemical characterization of the oligopeptide transport system of Lactococcus lactis [J]. J Bacteriol,1993,175:7523-7532
101 Gitton C., Meyrand M., Wang J., Caron C., Trubuil A., Guillot A., Mistou M. Y. Proteomic signature of Lactococcus lactis NCDO763 cultivated in milk [J]. App Env Microbiol,2005,71:7152-7163
102 Christensen J. E., Dudley E.G., Pederson J. A., Steele J. L. Peptidases and amino acid catabolism in lactic acid bacteria [J]. Ant Van Leeuw,1999,76:217-246
103 Derzelle S., Bolotin A., Mistou M. Y., Rul F. Proteome analysis of Streptococcus thermophilus grown in milk reveals pyruvate formate-lyase as the major upregulated protein [J]. Appl Environ Microbiol,2005,71 (12):8597-8605
104 den Hengst C.D., Groeneveld M., Kuipers O. P., Kok J. Identification and functional characterization of the Lactococcus lactis CodY-regulated branched-chain amino acid permease BcaP (CtrA) [J]. J Bacteriol,2006,188:3280-3289
105 Stucky K., Hagting A., Klein J.R., Matern H., Henrich B., Konings W. N., Plapp R. Cloning and characterization of brnQ, a gene encoding a low-affinity, branched-chain amino acid carrier in Lactobacillus delbruckii subsp. lactis DSM7290 [J]. Mol Gen Genet,1995,249:682-690
106 Matsubara K., Ohnishi K., Kiritani K. Nucleotide sequences and characterization of liv genes encoding components of the high-affinity branched-chain amino acid transport system in Salmonella typhimurium [J]. J Biochem,1992,112:93-101
107 Hebert E.M., De Giori G.S., Raya R. R. Isolation and characterization of a slowly milk-coagulating variant of Lactobacillus helveticus deficient in purine biosynthesis [J]. Appl Environ Microbiol,2001,67:1846-1850.
108 Dickely F., Nilsson D., Hansen E.B., Johansen E. solation of Lactococcus lactis nonsense suppressors and construction of a food-grade cloning vector [J]. Mol Microbiol,1995,15:839-847
109 BeyerN H., Roepstorff P., Hammer K., Kilstrup M. Proteome analysis of the purine stimulon from Lactococcus lactis [J]. Proteomics,2003,3(5):786-797
110 Gitton C., Meyrand M., Wang J. H., Caron C., Trubuil A., Guillot A., Mistou M. Y. Proteomic signature of Lactococcus lactis NCD0763 cultivated in milk [J]. Appl Environ Microbiol,2005,71(11):7152-7163
111 Beyer N. H., Roepstorff P., Hammer K., Kilstrup M. Proteome analysis of the purine stimulon from Lactococcus lactis [J]. Proteomics,2003,3:786-797
112 Herve-Jimenez L., Guillouard I., Guedon E., Boudebbouze S., et al. Postgenomic analysis of streptococcus thermophilus cocultivated in milk with Lactobacillus delbrueckii subsp. bulgaricus:involvement of nitrogen, purine, and iron metabolism. Appl Environ Microbiol,2009,75:2062-2073
113 Gitton C., Meyrand M., Wang J., Caron C., et al. Proteomic signature of Lactococcus lactls NCDO763 cultivated in milk [J]. Appl Environ Microbiol,2005,71:7152-7163
114 Postma P. W., Lengeler J. W., and Jacobson G. R. Phosphoenol-pyruvate:carbohydrate phosphotransferase systems of bacteria [J]. Microbiol Rev,1993,57:543-94
115 Simoni R. D., Levinthal M., Kundig F. D., Kundig W., Anderson B., Hartman P. E., Roseman S. Genetic evidence for the role of a bacterial phosphotransferase system in sugar transport [J]. Proc Natl Acad Sci U S A,1967,58:1963-1970
116 Reizer J., Saier M. H. Jr. Modular multidoma in phosphoryltransfer proteins of bacteria [J]. Curr Opin Struct Biol,1997,7:407-415
117 Saier M. H. Jr. Protein phosphorylation and allosteric control of inducer exclusion and catabolite repression by the bacterial phosphoenol-pyruvate:sugar phosphotransferase system [J]. Microbiol Rev,1989,53:109-120
118 Saier M. H. Jr., Reizer J. The bacterial phosphotransferase system:new frontiers 30 years later [J]. Mol Microbiol,1994,13:755-764
119 Lengeler J.W., Jahreis K. Phosphotransferase systems or PTSs as carbohydrate transport and as signal transduction systems [J]. Handbook of biological physics, 1996,2:573-598
120 Cohen D. P., Renes J., Bouwman F. G., Zoetendal E. G., Mariman E., de Vos W. M., Vaughan E. E. Proteomic analysis of log to stationary growth phase Lactobacillus plantarum cells and a 2-DE database [J]. Proteomics,2006,6:6485-6493
121 Herve-Jimenez L., Guillouard I., Guedon E., Gautier C., Boudebbouze S., Hols P., Monnet V., Rul F., Maguin E. Physiology of Streptococcus thermophilus during the late stage of milk fermentation with special regard to sulfur amino-acid metabolism [J]. Proteomics,2008,8:4273-4286
122 Gao H, Jiang X, Pogliano K, Aronson A. The Elbeta and E2 subunits of the Bacillus subtilis pyruvate dehydrogenase complex are involved in regulation of sporulation [J]. J Bacteriol,2002,184:2780-2788
123 McLeod A., Zagorec M., Champomier-Verges M. C., Naterstad K., Axelsson L. Primary metabolism in Lactobacillus sakei food isolates by proteomic analysis [J]. BMC Microbiol,2006,10:120
124 Duche O., Tremoulet F., Glaser P., Labadie J. Salt stress proteins induced in Listeria monocytogenes [J]. App Env Microbiol,2002,68:1491-1498
125 Salotra P., Singh D. K., Seal K.P., Krishna N., Jaffe H., Bhatnagar R. Expression of DnaK and GroEL homologs in Leuconostoc esenteroides in response to heat shock, cold shock or chemical stress [J]. FEMS Microbiol Lett,1995,131:57-62
126 Larsen N., Boye M., Siegumfeldt H., Jakobsen M. Differential expression of proteins and genes in the lag phase of Lactococcus lactis subsp. lactis grown in synthetic medium and reconstituted skim milk [J]. Appl Env Microbiol,2006,72:1173-1179
127 Martin M. G., Sender P. D., Peiru S., de Mendoza D., Magni C. Acid-inducible transcription of the operon encoding the citrate lyase complex of Lactococcus lactis Biovar diacetylactis CRL264 [J]. J Bacteriol,2004,186:5649-5660
128 Stulke J., Arnaud M., Rapoport G., Martin-Verstraete I. PRD—a protein domain involved in PTS-dependent induction and carbon catabolite repression of catabolic operons in bacteria [J]. Mol Microbiol,1998,28:865-874
129 Saulnier D. M., Molenaar D., de Vos W. M., Gibson G. R., Kolida S. Identification of prebiotic fructooligosaccharide metabolism in Lactobacillus plantarum WCFS1 through microarrays [J]. Appl Environ Microbiol,2007,73:1753-1765
130 Redon E., Loubiere P., Cocaign-Bousquet M. Transcriptome analysis of the progressive adaptation of Lactococcus lactis to carbon starvation [J]. J Bacteriol,2005,187: 3589-3592
131 Sheng J., Marquis R.E.Malolactic fermentation by Streptococcus mutans [J]. FEMS Microbiol Lett,2007,272:196-201
132 Frees D., Savijoki K., Varmanen P., Ingmer H. Clp ATPases and ClpP proteolytic complexes regulate vital biological processes in low GC, Grampositive bacteria[J]. Mol Microbiol,2007,63:1285-1295
133 Lim E. M., Smokvina T., Chervaux C., Ehrlich S. D., Maguin E. Seventh symposium on lactic acid bacteria. Genetics, Metabolism and Applications [J]. FEMS,2002, p85
134 Chan E., Weiss B. Endonuclease Ⅳ of Escherichia coli is induced by paraquat [J]. Proc Natl Acad Sci U S A,1987,84:3189-3193