258 Zhuoyang Zhang et al. /Acta Microbiologica Sinica (2008) 48(2) 表 1 Table 1 [4, 5] 益生菌的分类及其安全情况 Classification of probiotic organisms Organism Lact

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1 Mini-Review 小型综述 Acta Microbiologica Sinica 48(2) 257~261; 4 February 2008 ISSN ; CN /Q 益生菌的安全性 * 张灼阳, 刘畅, 郭晓奎 (, ) 摘要 :,,, ; ;,,,,, 关键词 ; ; 中图分类号 Q939.9 文献标识码 A 文章编号 (2008) [1], [2], (Lactic acid bacteria LAB), [3],, 70,,,, 1 益生菌的安全性现状及研究进展 (Lactobacillus) (Enterococcus),, 1 ;,,,,,, * Tel/Fax: xkguo@shsmu.edu.cn 作者简介 : (1984 ) sakuyaandy@163.com 收稿日期 : ; 修回日期 :

2 258 Zhuoyang Zhang et al. /Acta Microbiologica Sinica (2008) 48(2) 表 1 Table 1 [4, 5] 益生菌的分类及其安全情况 Classification of probiotic organisms Organism Lactobacillus Lactococcus Leuconostoc Streptococcus Enterococcus Bifidobacterium Saccharomyces Infection potential Mainly non-pathogens, some opportunistic infections (usually in immunocompromised patients) Mainly non-pathogens Mainly non-pathogens, some isolated cases of infection Oral streptococci mainly non-pathogens (including Streptococcus thermophilus); some may cause opportunistic infections Some strains are opportunistic pathogens with haemolytic activity and antibiotic resistance Mainly non-pathogens, some isolated cases of human infection Mainly non-pathogens, some isolated cases of human infection,, 1.1 益生菌潜在感染能力,, [4,6~8] 1999, (L. rhamnosus) 74,,, 4 0.5L L. rhamnosus GG LGG [9] 67,,, (Lactobacillus acidophils) (Streptococcus faecalis) [10] Saxelin 8509, 20 [7,8],, [11], ( ), Harty 5 16,, [12] 1.2 益生菌的代谢和酶对机体的影响 D- 2006, 5, 2, D-, 2, ( ), D-, D- [13],, D- [14] 1.2.2,,, [15],, N- [16],

3 / (2008) 48(2) 259 [17] (Clostridia) 1.2.3,, [17],,, [18],,,, , (Bacteroides spp.) [19] [20], [21], -7-, ph, , [22], 1.3 益生菌的免疫效应 1988,,, [23], 1991 McConnel, ( - ),, [24] 1993 Schwabb,,,,,,, [25],, 1.4 益生菌的耐药性 60,,,,,,, (Lb.acidophilus), (Lb.plantarum), (Lb.casei), (Lb.salivarius) (Lb.leishmannii) [26,27],,,,, [28, 29],, 25, [29], pamβ1 pip501 [30, 31]

4 260 Zhuoyang Zhang et al. /Acta Microbiologica Sinica (2008) 48(2), [32] 2 评估益生菌安全性的方法 ; (,,, ); [24],,,,,,, [33], 2.1 在体外和动物中的研究,,, [24] 2.2 对健康志愿者和临床试验的研究 [34~36], [37], 3 结论,,,,, LAB,,,, ; D-,,,, 参考文献 [1] FAO/WHO, Report on joint FAO/WHO expert consultation on evaluation of health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria [2] Isolauri E, Kirjavainen PV,Salminen S. Probiotics: a role in the treatment of intestinal infection and inflammation? Gut, Suppl 3: p. III54 9. [3],,.. (Chinese Journal of Microecolog), 2005, 17(1): 79. [4] Gasser F. Safety of lactic acid bacteria and their occurrence in human clinical infections. Bull Inst Pasteur, 1994, 92: [5] Donohue DC, Salminen S. Safety assessment of probiotic bacteria. Asia Pac J Clin Nutr, 1996, 5: [6] Aguirre M,Collins MD. Lactic acid bacteria and human clinical infection. J Appl Bacteriol, 1993, 75(2): [7] Saxelin M. Colonization of the human gastrointestinal tract by probiotic bacteria. Nutr Today, 1996, 31: 5S 8S. [8] Saxelin M, Chuang NH, Chassy B, et al. Lactobacilli and bacteremia in southern Finland, Clin Infect Dis, (3): [9] Rautio M, Jousimies-Somer H, Kauma H, et al. Liver abscess due to a Lactobacillus rhamnosus strain indistinguishable from L. rhamnosus strain GG. Clin Infect Dis, 1999, 28(5): [10] Mackay AD, Taylor MB, Kibbler CC, et al. Lactobacillus endocarditis caused by a probiotic organism. Clin Microbiol Infect, 1999, 5(5): [11] Horwitch CA, Furseth HA, Larson AM, et al. Lactobacillemia in three patients with AIDS. Clin Infect Dis, 1995, 21(6): [12] Harty DW, Oakey HJ, Patrikakis M, et al. Pathogenic potential

5 / (2008) 48(2) 261 of lactobacilli. Int J Food Microbiol, 1994, 24(1-2): [13] WH_Ku. Probiotics Provoked D-lactic Acidosis in Short Bowel Syndrome: Case Report and Literature Review. HK J Paediatr (New Series), 2006, 11: [14] Coronado BE, Opal SM,Yoburn DC. Antibiotic-induced D-lactic acidosis. Ann Intern Med, 1995, 122(11): [15] Packer PJ. ed. Nitrate Pharmacology and Toxicology. London:Taylor and Francis Ltd,1995. [16] Leach SA. ed. N-nitroso Compounds. London:Taylor and Francis Ltd, [17] Hill MJ. ed. Metabolism of Nitrogen Compounds: Miscellaneous Compounds. London:Taylor and Francis Ltd, [18] Sumner SS, Speckhard MW, Somers EB, et al. Isolation of histamine-producing Lactobacillus buchneri from Swiss cheese implicated in a food poisoning outbreak. Appl Environ Microbiol, 1985,50(4): [19] Hill MJ. ed. Bacteria and Fat Digestion. London:Taylor and Francis Ltd, [20] Bateup JM, McConnell MA, Jenkinson HF, et al. Comparison of Lactobacillus strains with respect to bile salt hydrolase activity, colonization of the gastrointestinal tract, and growth rate of the murine host. Appl Environ Microbiol, 1995, 61(3): [21] Low-Beer TS. Enterohepatic Circulation of Bile Salts. Lancet, 1998, 351: 613. [22] Zhou JS, Shu Q, Rutherfurd KJ, et al. Acute oral toxicity and bacterial translocation studies on potentially probiotic strains of lactic acid bacteria. Food Chem Toxicol, 2000, 38(2-3): [23] Sartor RB, Bond TM,Schwab JH. Systemic uptake and intestinal inflammatory effects of luminal bacterial cell wall polymers in rats with acute colonic injury. Infect Immun, 1988, 56(8): [24] Salminen S, von Wright A, Morelli L, et al. Demonstration of safety of probiotics -- a review. Int J Food Microbiol, 1998, 44(1-2): [25] Schwab JH. Phlogistic properties of peptidoglycan- polysaccharide polymers from cell walls of pathogenic and normal-flora bacteria which colonize humans. Infect Immun, 1993, 61(11): [26] Devriese LA,Butaye P. Vancomycin susceptibility an an aid to the identification of lactobacilli. Lett Appl Microbiol, 1998, 27(2): 121. [27] Elisha BG,Courvalin P. Analysis of genes encoding D-alanine:D-alanine ligase-related enzymes in Leuconostoc mesenteroides and Lactobacillus spp..gene, 1995, 152(1): [28] Mathur S,Singh R. Antibiotic resistance in food lactic acid bacteria--a review. Int J Food Microbiol, 2005, 105(3): [29] Wang TT,Lee BH. Plasmids in Lactobacillus. Crit Rev Biotechnol, 1997, 17(3): [30] Tannock GW. Conjugal transfer of plasmid pam beta 1 in Lactobacillus reuteri and between lactobacilli and Enterococcus faecalis. Appl Environ Microbiol, 1987, 53(11): [31] Langella P, Le Loir Y, Ehrlich SD, et al. Efficient plasmid mobilization by pip501 in Lactococcus lactis subsp. lactis. J Bacteriol, (18): [32] Clewell DB. ed. Bacterial Conjugation. New York:Plenum Press,1993. [33] Tang P, Foubister V, Pucciarelli MG, et al. Methods to study bacterial invasion. J Microbiol Methods, 1993, 18: [34] Lidbeck A, Edlund C, Gustafsson J A, et al. Impact of Lactobacillus acidophilus on the normal intestinal microflora after administration of two antimicrobial agents. Infection, 1988, 16(6): [35] Lidbeck A, Gustafsson JA,Nord CE. Impact of Lactobacillus acidophilus supplements on the human oropharyngeal and intestinal microflora. Scand J Infect Dis, 1987, 19(5): [36] Orrhage K, Brismar B, Nord CE. Effect of supplements with Bifidobacterium longum and Lactobacillus acidophiluson the intestinal microbiota during administration of clindamycin. Microb Ecol Health Dis, 1994, 7: [37] McFarland L, Bernasconi P. Saccharomyces boulardii: a review of an innovative biotherapeutic agent. Microbial Health Ecol Dis, 1993, 6: Safety of probiotics A Review Zhuoyang Zhang, Chang Liu, Xiaokui Guo * (Department of Microbiology and Parasitology, Shanghai Jiaotong University, School of Medicine, Shanghai , China) Abstract: Probiotics are live microorganisms. When they were administered in adequate amounts, they could have beneficial effects on the host. They are generally applied in food fermentation, industrial lactic acid production and medical care. With the appearance of commercial probiotics, more concerns were raised on the safety of probiotics. At present, there were four aspects of safety concerns on probiotics: pathogenicity and infectivity; deleterious metabolic activities; excessive immune response and potential gene transfer. Conventional toxicology and safety evaluation has limited value in the safety assessment of probiotics used in marketing food and drugs nowadays. Instead, multidisciplinary approaches are necessary for the systematical safety evaluation of probiotic strains. It may involve genomics, metabolismics, proteomics, among others. The toxigenic metabolic activity should be considered especially. We reviewed recent developments and research methods on the safety of probiotics. Safety evaluation of the lactic acid bacteria for human consumption must be assessed by proposing criteria standards, guidelines and regulations, for better applications for consumers. Keywords: probiotics; Lactic acid bacteria (LAB); safety; deleterious metabolic activities * Corresponding author. Tel/Fax: ; xkguo@shsmu.edu.cn Received:24 May 2007/Revised:17 October 2007