益生菌胞外蛋白与肠道粘膜免疫细胞互作关系的研究进展
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摘要
近期国内外研究证实了益生菌分泌的胞外蛋白具有增强粘膜屏障、调节免疫、维持肠道稳态的功能,在一定程度上可以改善、缓解和治疗肠道疾病。益生菌分泌的胞外蛋白对肠粘膜免疫作用及对机体健康的影响的相关阐述已成为人们关注的热点,为探究益生菌对肠粘膜屏障及粘膜免疫信号通路的功能表现的分子基础,本文首先概括肠粘膜系统及其免疫机制和益生菌分泌胞外蛋白的作用,然后重点介绍国内外对分泌胞外蛋白的益生菌的相关研究进展,并指出胞外蛋白将在一定程度上打通肠粘膜免疫信号通路途径,发挥治疗肠道疾病的作用,从而达到维护肠道健康的目的,也为解决肠道健康问题提供了一条可行的途径。
Recent studies home and abroad have confirmed that these extracellular proteins have the function of enhancing mucosal barrier,regulating immune and maintaining intestinal homeostasis. And to a certain extent,these also can improve,relieve and treat intestinal diseases.The relevant exposition of probiotics secreted extracellular proteins on the intestinal mucosal immune function and the impact on the health has become a research focus.In order to explore the molecular basis of probiotics on the functional barrier of intestinal mucosal barrier and mucosal immune signal,the intestinal mucosal system and its immune mechanism and the role of probiotics in the secretion of extracellular proteins were first summarized,and then the domestic and foreign research on probiotics secreting extracellular proteins was highlighted,and the opinion that extracellular proteins would break through the intestinal mucosal immune signal pathways and played a role in the treatment of intestinal diseases so as to achieve the purpose of maintaining intestinal health was put forward in this article.At the same time,it also put forward a viable approach for research and development to solve the problem of intestinal health.
Recent studies home and abroad have confirmed that these extracellular proteins have the function of enhancing mucosal barrier,regulating immune and maintaining intestinal homeostasis. And to a certain extent,these also can improve,relieve and treat intestinal diseases.The relevant exposition of probiotics secreted extracellular proteins on the intestinal mucosal immune function and the impact on the health has become a research focus.In order to explore the molecular basis of probiotics on the functional barrier of intestinal mucosal barrier and mucosal immune signal,the intestinal mucosal system and its immune mechanism and the role of probiotics in the secretion of extracellular proteins were first summarized,and then the domestic and foreign research on probiotics secreting extracellular proteins was highlighted,and the opinion that extracellular proteins would break through the intestinal mucosal immune signal pathways and played a role in the treatment of intestinal diseases so as to achieve the purpose of maintaining intestinal health was put forward in this article.At the same time,it also put forward a viable approach for research and development to solve the problem of intestinal health.
引文
[1]Amer M,Nadeem M,Nazir S,et al.Probiotics and their use in inflammatory bowel disease[J].Alternative Therapies in Health&Medicine,2017.
[2]Wischmeyer PE,Ichim TE,Radecka I,et al.Advances in probiotic bacteria[M].New York,2017:1-22.
[3]Lilly D M,Stillwell R H.Probiotics:Growth-promoting factors produced by microorganisms[J].Science,1965,147:747-748.
[4]Kumar M,Babaei P,Ji B,et al.Human gut microbiota and healthy aging:Recent developments and future prospective[J].Nutrition&Healthy Aging,2016,4(1):3-16.
[5]Stritzker J,Weibel S,Hill P J,et al.Tumor-specific colonization,tissue distribution,and gene induction by probiotic Escherichia coli Nissle 1917 in live mice[J].Int J Med Microbiol2007,297:151-162.
[6]Xu Y F,Zhu L P,Hu B,et al.A new expression plasmid in Bifidobacterium longum as adelivery system of endostatin for cancer gene therapy[J].Cancer Gene Ther 2007,14:151-157.
[7]王友湘,陈庆森.益生菌和肠道粘膜免疫关系的研究进展[J].食品科学,2007,28(8):537-542.
[8]朱晨晨,陈庆森.乳源酪蛋白糖巨肽改善炎症性肠病的研究进展[J].食品科学,2012,33(1):262-266.
[9]Perezlopez A,Behnsen J,Nuccio S P,et al.Mucosal immunity to pathogenic intestinal bacteria[J].Nature Reviews Immunology,2016,16(3):135.
[10]Wan L Y,Chen Z J,Shah N P,et al.Modulation of intestinal epithelial defense responses by probiotic bacteria[J].Critical Reviews in Food Science&Nutrition,2016,56(16):2628.
[11]杜瑞亭,托娅,张和平.干酪乳杆菌Zhang对小鼠肠道免疫功能的影响[J].营养学报,2009,31(4):396-399.
[12]张凤娟,孙正芸,程蓓蕾.口服益生菌对早产儿消化道及免疫功能的影响[J].山东大学学报(医学版),2008,46(11):1069-1071.
[13]郝小燕,赵卫,曹虹.益生菌对肠道致病菌肠粘附抑制作用[J].中国公共卫生,2010,26(12):1516-1518.
[14]陈红旗,杨俊,周玉坤.益生菌对炎性肠病小鼠肠屏障功能的影响[J].中国普外基础与临床杂志,2011,18(12):1242-1247.
[15]Sánchez B,Delgado S,Blanco Míguez A,et al.Probiotics,gut microbiota,and their influence on host health and disease[J].Molecular Nutrition&Food Research,2016,61(1).
[16]Sánchez B,Bressollier P,Urdaci M C.Exported proteins in probiotic bacteria:adhesion to intestinal surfaces,host immunomodulation and molecular cross-talking with the host[J].Fems Immunol Med Microbiol,2008,54(1):1-17.
[17]Sánchez B,Chaignepain S,Schmitter J M,et al.A method for the identification of proteins secreted by lactic acid bacteria grown in complex media[J].Fems Microbiology Letters,2009,295(2):226-229.
[18]Wely K H M V,Swaving J,Freudl R,et al.Translocation of proteins across the cell envelope of Gram-positive bacteria[J].Fems Microbiology Reviews,2001,25(4):437-454.
[19]Natale P,Brüser T,Driessen A J.Sec-and Tat-mediated protein secretion across the bacterial cytoplasmic membranedistinct translocases and mechanisms[J].Biochimica Et Biophysica Acta,2008,1778(9):1735-1756.
[20]Dicksved J.Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn’s disease[J].Inflammatory Bowel Diseases,2009,15(5):653-660.
[21]Heijne G V,Abrahmsèn L.Species-specific variation in signal peptide design Implications for protein secretion in foreign hosts[J].Febs Letters,1989,244(2):439-446.
[22]Jeffery C J.Moonlighting proteins:old proteins learning new tricks[J].Trends in Genetics Tig,2003,19(8):415.
[23]Hoarau C,Martin L,Faugaret D,et al.Supernatant from Bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells[J].Plos One,2008,3(7):e2753.
[24]Underhill D M,Ozinsky.A Toll-like receptors:Key mediators of microbe detection[J].Curr Opin Immunol,2002,14:103-110.
[25]Gewirtz A T.Flag in the crossroads:flagellin modulates innate and adaptive immunity[J].Current Opinion in Gastroenterology,2006,22(1):8-12.
[26]Konstantinov S R,Smidt H,Vos W M D,et al.S Layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions[J].Proceedings of the National Academy of Sciences of the United States of America,2008,105(49):19474.
[27]Yan F,Cao H,Cover T L,et al.Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth[J].Gastroenterology,2007,132(2):562-575.
[28]Sánchez B,Schmitter J M,Urdaci M C.Identification of novel proteins secreted by Lactobacillus rhamnosus GG grown in de Mann-Rogosa-Sharpe broth[J].Letters in Applied Microbiology,2009,48(5):618-622.
[29]Tao Y,Drabik K A,Waypa T S,et al.Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells[J].American Journal of Physiology Cell Physiology,2006,290(4):C1018.
[30]Beck H C,Madsen S M,Glenting J,et al.Proteomic analysis of cell surface-associated proteins from probiotic Lactobacillus plantarum[J].FEMS Microbiology Letters,2010,297(1):61-66.
[31]Bernardo D,Sánchez B,Alhassi H O,et al.Microbiota/host crosstalk biomarkers:Regulatory response of human intestinal dendritic cells exposed to,Lactobacillus,extracellular encrypted peptide[J].Plos One,2012,7(5):e36262.
[32]贾彦,任效东,江岩,等.嗜酸乳杆菌胞外蛋白的分离纯化及抑制HT-29细胞增殖作用的研究[J].现代食品科技,2016(11):56-62.
[33]王泳,贾彦,任效东,等.嗜酸乳杆菌胞外蛋白调控MAPK和PI3K-AKT信号途径关键蛋白活化水平[J].食品科学,2017,38(3):155-163.
[34]陈庆森,任效东,阎亚丽.一种乳酸菌胞外蛋白的提取方法及应用:中国,104388503 A[P].2015.
[35]Schlee M,Harder J,K9ten B,et al.Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2[J].Clinical&Experimental Immunology,2008,151(3):528.
[36]Carmo F L R D,Rabah H,Huang S,et al.Propionibacterium freudenreichii surface protein Slp B is involved in adhesion to intestinal HT-29 Cells[J].Frontiers in Microbiology,2017,8.
[37]Mitsuma T,Odajima H,Momiyama Z,et al.Enhancement of gene expression by a peptide p(CHWPR)produced by Bifidobacterium lactis BB-12[J].Microbiology&Immunology,2008,52(3):144-155.
[38]Ewaschuk J B,Diaz H,Meddings L,et al.Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function[J].Am J Physiol Gastrointest Liver Physiol,2008,295:G1025-G1034.
[39]Gilad O,Svensson B,Viborg A H,et al.The extracellular proteome of Bifidobacterium animalis subsp.lactis BB-12 reveals proteins with putative roles in probiotic effects[J].PROTEOMICS,2011,11(12):2503-2514.
[40]Ivanov D,Emonet C,Foata F,et al.A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastaselike serine proteases[J].Journal of Biological Chemistry,2006,281(25):17246-17252.
[41]Grozdanov L,Raasch C,Schulze J,et al.Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917[J].J Bacteriol,2004,186,5432-5441.
[42]Schultz M.Clinical use of E.coli Nissle 1917 in inflammatory bowel disease[J].Inflamm Bowel Dis,2008,14:1012-1018.
[43]Schlee M,Wehkamp J,Altenhoefer A,et al.Induction of human beta-defensin2 by the probiotic Escherichia coli Nissle1917 is mediated through flagellin[J].Infect Immun,2007,75:2399-2407.
[44]贾彦,李毛毛,陈蕊,等.杜仲水提液对嗜酸乳杆菌生长及发酵产物的影响[J].食品科学,2016,37(23):147-153.
[45]Kim H J,Camilleri M,Mckinzie S,et al.A randomized controlled trial of a probiotic,VSL#3,on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome[J].Alimentary Pharmacology&Therapeutics,2003,17(7):895-904.
[46]Tursi A,Brandimarte G,Papa A,et al.Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment:A doubleblind,randomized,placebo-controlled study[J].American Journal of Gastroenterology,2010,105(10):2218.
[47]Arumugam Velayudham,Angela Dolganiuc,Michael Ellis,et al.VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced NASH model in mice[J].Hepatology,2009,49(3):989-997.
[48]Caballerofranco C,Keller K,De S C,et al.The VSL#3probiotic formula induces mucin gene expression and secretion in colonic epithelial cells[J].American Journal of Physiology Gastrointestinal&Liver Physiology,2007,292(1):G315.
[49]Madsen K L,Malfair D,Gray D,et al.Interleukin-10 genedeficient mice develop a primary intestinal permeability defect in response to enteric microflora[J].Inflamm Bowel Dis,1995:262-270.
[50]Bousvaros A,Guandalini S,Baldassano R N,et al.A randomized,double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease[J].Inflammatory Bowel Diseases,2005,11(9):833-839.
[51]Berger R E.Lactobacillus sepsis associated with probiotic therapy[J].Pediatrics,2006,115(1):178.
[52]Apostolou E,Kirjavainen P V,Saxelin M,et al.Good adhesion properties of probiotics:A potential risk for bacteremia[J].Fems Immunology&Medical Microbiology,2001,31(1):35.
[2]Wischmeyer PE,Ichim TE,Radecka I,et al.Advances in probiotic bacteria[M].New York,2017:1-22.
[3]Lilly D M,Stillwell R H.Probiotics:Growth-promoting factors produced by microorganisms[J].Science,1965,147:747-748.
[4]Kumar M,Babaei P,Ji B,et al.Human gut microbiota and healthy aging:Recent developments and future prospective[J].Nutrition&Healthy Aging,2016,4(1):3-16.
[5]Stritzker J,Weibel S,Hill P J,et al.Tumor-specific colonization,tissue distribution,and gene induction by probiotic Escherichia coli Nissle 1917 in live mice[J].Int J Med Microbiol2007,297:151-162.
[6]Xu Y F,Zhu L P,Hu B,et al.A new expression plasmid in Bifidobacterium longum as adelivery system of endostatin for cancer gene therapy[J].Cancer Gene Ther 2007,14:151-157.
[7]王友湘,陈庆森.益生菌和肠道粘膜免疫关系的研究进展[J].食品科学,2007,28(8):537-542.
[8]朱晨晨,陈庆森.乳源酪蛋白糖巨肽改善炎症性肠病的研究进展[J].食品科学,2012,33(1):262-266.
[9]Perezlopez A,Behnsen J,Nuccio S P,et al.Mucosal immunity to pathogenic intestinal bacteria[J].Nature Reviews Immunology,2016,16(3):135.
[10]Wan L Y,Chen Z J,Shah N P,et al.Modulation of intestinal epithelial defense responses by probiotic bacteria[J].Critical Reviews in Food Science&Nutrition,2016,56(16):2628.
[11]杜瑞亭,托娅,张和平.干酪乳杆菌Zhang对小鼠肠道免疫功能的影响[J].营养学报,2009,31(4):396-399.
[12]张凤娟,孙正芸,程蓓蕾.口服益生菌对早产儿消化道及免疫功能的影响[J].山东大学学报(医学版),2008,46(11):1069-1071.
[13]郝小燕,赵卫,曹虹.益生菌对肠道致病菌肠粘附抑制作用[J].中国公共卫生,2010,26(12):1516-1518.
[14]陈红旗,杨俊,周玉坤.益生菌对炎性肠病小鼠肠屏障功能的影响[J].中国普外基础与临床杂志,2011,18(12):1242-1247.
[15]Sánchez B,Delgado S,Blanco Míguez A,et al.Probiotics,gut microbiota,and their influence on host health and disease[J].Molecular Nutrition&Food Research,2016,61(1).
[16]Sánchez B,Bressollier P,Urdaci M C.Exported proteins in probiotic bacteria:adhesion to intestinal surfaces,host immunomodulation and molecular cross-talking with the host[J].Fems Immunol Med Microbiol,2008,54(1):1-17.
[17]Sánchez B,Chaignepain S,Schmitter J M,et al.A method for the identification of proteins secreted by lactic acid bacteria grown in complex media[J].Fems Microbiology Letters,2009,295(2):226-229.
[18]Wely K H M V,Swaving J,Freudl R,et al.Translocation of proteins across the cell envelope of Gram-positive bacteria[J].Fems Microbiology Reviews,2001,25(4):437-454.
[19]Natale P,Brüser T,Driessen A J.Sec-and Tat-mediated protein secretion across the bacterial cytoplasmic membranedistinct translocases and mechanisms[J].Biochimica Et Biophysica Acta,2008,1778(9):1735-1756.
[20]Dicksved J.Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn’s disease[J].Inflammatory Bowel Diseases,2009,15(5):653-660.
[21]Heijne G V,Abrahmsèn L.Species-specific variation in signal peptide design Implications for protein secretion in foreign hosts[J].Febs Letters,1989,244(2):439-446.
[22]Jeffery C J.Moonlighting proteins:old proteins learning new tricks[J].Trends in Genetics Tig,2003,19(8):415.
[23]Hoarau C,Martin L,Faugaret D,et al.Supernatant from Bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells[J].Plos One,2008,3(7):e2753.
[24]Underhill D M,Ozinsky.A Toll-like receptors:Key mediators of microbe detection[J].Curr Opin Immunol,2002,14:103-110.
[25]Gewirtz A T.Flag in the crossroads:flagellin modulates innate and adaptive immunity[J].Current Opinion in Gastroenterology,2006,22(1):8-12.
[26]Konstantinov S R,Smidt H,Vos W M D,et al.S Layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions[J].Proceedings of the National Academy of Sciences of the United States of America,2008,105(49):19474.
[27]Yan F,Cao H,Cover T L,et al.Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth[J].Gastroenterology,2007,132(2):562-575.
[28]Sánchez B,Schmitter J M,Urdaci M C.Identification of novel proteins secreted by Lactobacillus rhamnosus GG grown in de Mann-Rogosa-Sharpe broth[J].Letters in Applied Microbiology,2009,48(5):618-622.
[29]Tao Y,Drabik K A,Waypa T S,et al.Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells[J].American Journal of Physiology Cell Physiology,2006,290(4):C1018.
[30]Beck H C,Madsen S M,Glenting J,et al.Proteomic analysis of cell surface-associated proteins from probiotic Lactobacillus plantarum[J].FEMS Microbiology Letters,2010,297(1):61-66.
[31]Bernardo D,Sánchez B,Alhassi H O,et al.Microbiota/host crosstalk biomarkers:Regulatory response of human intestinal dendritic cells exposed to,Lactobacillus,extracellular encrypted peptide[J].Plos One,2012,7(5):e36262.
[32]贾彦,任效东,江岩,等.嗜酸乳杆菌胞外蛋白的分离纯化及抑制HT-29细胞增殖作用的研究[J].现代食品科技,2016(11):56-62.
[33]王泳,贾彦,任效东,等.嗜酸乳杆菌胞外蛋白调控MAPK和PI3K-AKT信号途径关键蛋白活化水平[J].食品科学,2017,38(3):155-163.
[34]陈庆森,任效东,阎亚丽.一种乳酸菌胞外蛋白的提取方法及应用:中国,104388503 A[P].2015.
[35]Schlee M,Harder J,K9ten B,et al.Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2[J].Clinical&Experimental Immunology,2008,151(3):528.
[36]Carmo F L R D,Rabah H,Huang S,et al.Propionibacterium freudenreichii surface protein Slp B is involved in adhesion to intestinal HT-29 Cells[J].Frontiers in Microbiology,2017,8.
[37]Mitsuma T,Odajima H,Momiyama Z,et al.Enhancement of gene expression by a peptide p(CHWPR)produced by Bifidobacterium lactis BB-12[J].Microbiology&Immunology,2008,52(3):144-155.
[38]Ewaschuk J B,Diaz H,Meddings L,et al.Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function[J].Am J Physiol Gastrointest Liver Physiol,2008,295:G1025-G1034.
[39]Gilad O,Svensson B,Viborg A H,et al.The extracellular proteome of Bifidobacterium animalis subsp.lactis BB-12 reveals proteins with putative roles in probiotic effects[J].PROTEOMICS,2011,11(12):2503-2514.
[40]Ivanov D,Emonet C,Foata F,et al.A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastaselike serine proteases[J].Journal of Biological Chemistry,2006,281(25):17246-17252.
[41]Grozdanov L,Raasch C,Schulze J,et al.Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917[J].J Bacteriol,2004,186,5432-5441.
[42]Schultz M.Clinical use of E.coli Nissle 1917 in inflammatory bowel disease[J].Inflamm Bowel Dis,2008,14:1012-1018.
[43]Schlee M,Wehkamp J,Altenhoefer A,et al.Induction of human beta-defensin2 by the probiotic Escherichia coli Nissle1917 is mediated through flagellin[J].Infect Immun,2007,75:2399-2407.
[44]贾彦,李毛毛,陈蕊,等.杜仲水提液对嗜酸乳杆菌生长及发酵产物的影响[J].食品科学,2016,37(23):147-153.
[45]Kim H J,Camilleri M,Mckinzie S,et al.A randomized controlled trial of a probiotic,VSL#3,on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome[J].Alimentary Pharmacology&Therapeutics,2003,17(7):895-904.
[46]Tursi A,Brandimarte G,Papa A,et al.Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment:A doubleblind,randomized,placebo-controlled study[J].American Journal of Gastroenterology,2010,105(10):2218.
[47]Arumugam Velayudham,Angela Dolganiuc,Michael Ellis,et al.VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced NASH model in mice[J].Hepatology,2009,49(3):989-997.
[48]Caballerofranco C,Keller K,De S C,et al.The VSL#3probiotic formula induces mucin gene expression and secretion in colonic epithelial cells[J].American Journal of Physiology Gastrointestinal&Liver Physiology,2007,292(1):G315.
[49]Madsen K L,Malfair D,Gray D,et al.Interleukin-10 genedeficient mice develop a primary intestinal permeability defect in response to enteric microflora[J].Inflamm Bowel Dis,1995:262-270.
[50]Bousvaros A,Guandalini S,Baldassano R N,et al.A randomized,double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease[J].Inflammatory Bowel Diseases,2005,11(9):833-839.
[51]Berger R E.Lactobacillus sepsis associated with probiotic therapy[J].Pediatrics,2006,115(1):178.
[52]Apostolou E,Kirjavainen P V,Saxelin M,et al.Good adhesion properties of probiotics:A potential risk for bacteremia[J].Fems Immunology&Medical Microbiology,2001,31(1):35.