期刊论文详细信息
Gut Pathogens
Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis
Anderson Miyoshi1  Ana Maria Caetano Faria2  Vasco Azevedo1  Jean Guy LeBlanc5  Denise Carmona Cara4  Kátia Moraes1  Marcela de Azevedo1  Vanessa Bastos Pereira1  Adna Luciana Sousa2  Luísa Lemos2  Déborah Nogueira Cruz2  Thais Garcias Moreira3  Clarissa Santos Rocha1  Ana Cristina Gomes-Santos2  Tessalia Diniz Luerce1 
[1] Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 – 31270-901 Belo Horizonte, MG, Brazil;Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;Departamento de Ciência de Alimentos, Faculdade de Farmácia, Belo Horizonte, MG, Brazil;Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;Centro de Referencia para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Argentina
关键词: Probiotics;    Regulatory T cells;    Cytokines;    Colitis;    Lactococcus lactis;   
Others  :  1133841
DOI  :  10.1186/1757-4749-6-33
 received in 2014-05-16, accepted in 2014-07-20,  发布年份 2014
PDF
【 摘 要 】

Background

Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis.

Methods

In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS).

Results

Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4+ T cells (Tregs) bearing surface TGF-β in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen.

Conclusions

Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

【 授权许可】

   
2014 Luerce et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150304183708141.pdf 1585KB PDF download
Figure 7. 34KB Image download
Figure 6. 77KB Image download
Figure 5. 63KB Image download
Figure 4. 58KB Image download
Figure 3. 118KB Image download
Figure 2. 66KB Image download
Figure 1. 50KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】
  • [1]Khor B, Gardet A, Xavier RJ: Genetics and pathogenesis of inflammatory bowel disease. Nature 2011, 474:307-317.
  • [2]LeBlanc JG, Aubry C, Cortes-Perez NG, de Moreno de LeBlanc A, Vergnolle N, Langella P, Azevedo V, Chatel J-M, Miyoshi A, Bermúdez-Humarán LG: Mucosal targeting of therapeutic molecules using genetically modified lactic acid bacteria: an update. FEMS Microbiol Lett 2013, 344(1):1-9.
  • [3]Podolsky DK: Inflammatory bowel disease. N Engl J Med 2002, 347:417-429.
  • [4]Marteau P: Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo controlled GETAID trial. Gut 2006, 55:842-847.
  • [5]Nielsen OH, Munck LK: Drug insight: aminosalicylates for the treatment of IBD. Nat Clin Pract Gastroenterol Hepatol 2007, 4:160-170.
  • [6]de Moreno de Leblanc A, Del Carmen S, Zurita-Turk M, Santos Rocha C, van de Guchte M, Azevedo V, Miyoshi A, LeBlanc JG: Importance of IL-10 modulation by probiotic microorganisms in gastrointestinal inflammatory diseases. ISRN Gastroenterol 2011, 2011:892971.
  • [7]Cronin M, Ventura M, Fitzgerald GF, van Sinderen D: Progress in genomics, metabolism and biotechnology of bifidobacteria. Int J Food Microbiol 2011, 149:4-18.
  • [8]Wescombe PA, Heng NC, Burton JP, Chilcott CN, Tagg JR: Streptococcal bacteriocins and the case for Streptococcus salivarius as model oral probiotics. Future Microbiol 2009, 4:819-835.
  • [9]Kühbacher T: Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis. Gut 2006, 55:833-841.
  • [10]Nanda Kumar NS, Balamurugan R, Jayakanthan K, Pulimood A, Pugazhendhi S, Ramakrishna BS: Probiotic administration alters the gut flora and attenuates colitis in mice administered dextran sodium sulfate. J Gastroenterol Hepatol 2008, 23:1834-1839.
  • [11]Castillo NA, DeMorenode LeBlanc A, de Moreno de LeBlanc AM, Galdeano C, Perdigón G: Comparative study of the protective capacity against Salmonella infection between probiotic and nonprobiotic Lactobacilli. J Appl Microbiol 2013, 114:861-876.
  • [12]Chai W, Burwinkel M, Wang Z, Palissa C, Esch B, Twardziok S, Rieger J, Wrede P, Schmidt MFG: Antiviral effects of a probiotic Enterococcus faecium strain against transmissible gastroenteritis coronavirus. Arch Virol 2013, 158:799-807.
  • [13]Isolauri E, Rautava S, Salminen S: Probiotics in the development and treatment of allergic disease. Gastroenterol Clin North Am 2012, 41:747-762.
  • [14]Madsen K, Cornish A, Soper P, McKaigney C, Jijon H, Yachimec C, Doyle J, Jewell L, De Simone C: Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology 2001, 121:580-591.
  • [15]Reiff C, Kelly D: Inflammatory bowel disease, gut bacteria and probiotic therapy. Int J Med Microbiol 2010, 300:25-33.
  • [16]Jijon HB, Panenka WJ, Madsen KL, Parsons HG: MAP kinases contribute to IL-8 secretion by intestinal epithelial cells via a posttranscriptional mechanism. Am J Physiol Cell Physiol 2002, 283:C31-C41.
  • [17]Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M: Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 2005, 174:3237-3246.
  • [18]Zhang L, Li N, Caicedo R, Neu J: Alive and dead Lactobacillus rhamnosus GG decrease tumor necrosis factor-alpha-induced interleukin-8 production in Caco-2 cells. J Nutr 2005, 135:1752-1756.
  • [19]Riedel CU, Foata F, Philippe D, Adolfsson O, Eikmanns BJ, Blum S: Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-kappaB activation. World J Gastroenterol 2006, 12:3729-3735.
  • [20]Santos Rocha C, Lakhdari O, Blottière HM, Blugeon S, Sokol H, Bermudez-Humaran LG, Azevedo V, Miyoshi A, Doré J, Langella P, Maguin E, van de Guchte M: Anti-inflammatory properties of dairy lactobacilli. Inflamm Bowel Dis 2012, 18:657-666.
  • [21]Kimoto H, Kurisaki J, Tsuji NM, Ohmomo S, Okamoto T: Lactococci as probiotic strains: adhesion to human enterocyte-like Caco-2 cells and tolerance to low pH and bile. Lett Appl Microbiol 1999, 29:313-316.
  • [22]Nishitani Y, Tanoue T, Yamada K, Ishida T, Yoshida M, Azuma T, Mizuno M: Lactococcus lactis subsp. cremoris FC alleviates symptoms of colitis induced by dextran sulfate sodium in mice. Int Immunopharmacol 2009, 9:1444-1451.
  • [23]Faria AM, Weiner HL: Oral tolerance. Immunol Rev 2005, 206:232-259.
  • [24]Hoffmann E, Dittrich-Breiholz O, Holtmann H, Kracht M: Multiple control of interleukin-8 gene expression. J Leukoc Biol 2002, 72:847-855.
  • [25]Wang S, Liu Z, Wang L, Zhang X: NF-kappaB signaling pathway, inflammation and colorectal cancer. Cell Mol Immunol 2009, 6:327-334.
  • [26]Grimm MC, Elsbury SK, Pavli P, Doe WF: Interleukin 8: cells of origin in inflammatory bowel disease. Gut 1996, 38(1):90-98.
  • [27]Neurath MF, Pettersson S, Buschenfelde KH M z, Strober W: Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Nat Med 1996, 2:998-1004.
  • [28]Ma D, Forsythe P, Bienenstock J: Live Lactobacillus rhamnosus [corrected] is essential for the inhibitory effect on tumor necrosis factor alpha-induced interleukin-8 expression. Infect Immun 2004, 72:5308-5314.
  • [29]Bai AP, Ouyang Q, Zhang W, Wang CH, Li SF: Probiotics inhibit TNF-alpha-induced interleukin-8 secretion of HT29 cells. World J Gastroenterol 2004, 10:455-457.
  • [30]Malin M, Suomalainen H, Saxelin M, Isolauri E: Promotion of IgA immune response in patients with Crohn's disease by oral bacteriotherapy with Lactobacillus GG. Ann Nutr Metab 1996, 40:137-145.
  • [31]O'Sullivan DJ: Screening of intestinal microflora for effective probiotic bacteria. J Agric Food Chem 2001, 49:1751-1760.
  • [32]Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R: A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 1990, 98:694-702.
  • [33]Laroui H, Ingersoll SA, Liu HC, Baker MT, Ayyadurai S, Charania MA, Laroui F, Yan Y, Sitaraman SV, Merlin D: Dextran Sodium Sulfate (DSS) Induces Colitis in Mice by Forming Nano-Lipocomplexes with Medium-Chain Length Fatty Acids in the Colon. PLoS One 2012, 7(3):e32084.
  • [34]Kimoto H, Mizumachi K, Okamoto T, Kurisaki J: New Lactococcus strain with immunomodulatory activity: enhancement of Th1-type immune response. Microbiol Immunol 2004, 48:75-82.
  • [35]Pavan S, Desreumaux P, Mercenier A: Use of mouse models to evaluate the persistence, safety, and immune modulation capacities of lactic acid bacteria. Clin Diagn Lab Immunol 2003, 10:696-701.
  • [36]Podolsky DK: Mucosal immunity and inflammation. V. Innate mechanisms of mucosal defense and repair: the best offense is a good defense. Am J Physiol 1999, 277:G495-G499.
  • [37]Dann SM, Spehlmann ME, Hammond DC, Iimura M, Hase K, Choi LJ, Hanson E, Eckmann L: IL-6-dependent mucosal protection prevents establishment of a microbial niche for attaching/effacing lesion-forming enteric bacterial pathogens. J Immunol 2008, 180:6816-6826.
  • [38]Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, Scheller J, Rose-John S, Cheroutre H, Eckmann L, Karin M: IL-6 and STAT3 are required for survival of intestinal epithelial cells and development of colitis associated cancer. Cancer Cell 2009, 16:103-113.
  • [39]Chalaris A, Adam N, Sina C, Rosenstiel P, Lehmann-Koch J, Schirmacher P, Hartmann D, Cichy J, Gavrilova O, Schreiber S, Jostock T, Matthews V, Hasler R, Becker C, Neurath MF, Reiss K, Saftig P, Scheller J, Rose-John S: Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice. J Exp Med 2010, 207:1617-1624.
  • [40]Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S: The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011, 1813(5):878-888.
  • [41]Shen W, Durum SK: Synergy of IL-23 and Th17 cytokines: new light on inflammatory bowel disease. Neurochem Res 2010, 35:940-946.
  • [42]Ogawa A, Andoh A, Araki Y, Bamba T, Fujiyama Y: Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol 2004, 110:55-62.
  • [43]Gomes-Santos AC, Moreira TG, Castro-Junior AB, Horta BC, Lemos L, Cruz DN, Guimarães MAF, Cara DC, McCafferty D-M, Faria AMC: New insights into the immunological changes in IL-10-deficient mice during the course of spontaneous inflammation in the gut mucosa. Clin Dev Immunol 2012, 2012:560817.
  • [44]Bouma G, Strober W: The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 2003, 3:521-533.
  • [45]Strober W, Fuss I, Mannon P: The fundamental basis of inflammatory bowel disease. J Clin Invest 2007, 117:514-521.
  • [46]Veltkamp C: Regulatory CD4 + CD25+ cells reverse imbalances in the T cell pool of bone marrow transplanted TGepsilon26 mice leading to the prevention of colitis. Gut 2005, 54:207-214.
  • [47]Chen W: Dendritic cells and (CD4+)CD25+ T regulatory cells: crosstalk between two professionals in immunity versus tolerance. Front Biosci 2006, 11:1360-1370.
  • [48]Coombes J, Powrie F: Dendritic cells in intestinal immune regulation. Nat Rev Immunol 2008, 8(6):435-446.
  • [49]Jeon SG, Kayama H, Ueda Y, Takahashi T, Asahara T, Tsuji H, Tsuji NM, Kiyono H, Ma JS, Kusu T, Okumura R, Hara H, Yoshida H, Yamamoto M, Nomoto K, Takeda K: Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon. PLoS Pathog 2012, 8:e1002714.
  • [50]Miyoshi A, Jamet E, Commissaire J, Renault P, Langella P, Azevedo V: A xylose-inducible expression system for Lactococcus lactis. FEMS Microbiol Lett 2004, 239:205-212.
  • [51]Chopin A, Chopin MC, Moillo-Batt A, Langella P: Two plasmid-determined restriction and modification systems in Streptococcus lactis. Plasmid 1984, 11:260-263.
  • [52]Gasson MJ: Plasmid complements of Streptococcus lactis NCDO 712 and other lactic streptococci after protoplast-induced curing. J Bacteriol 1983, 154:1-9.
  • [53]Cooper HS, Murthy SN, Shah RS, Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993, 69:238-249.
  • [54]McCafferty DM, Sihota E, Muscara M, Wallace JL, Sharkey KA, Kubes P: Spontaneously developing chronic colitis in IL-10/iNOS double-deficient mice. Am J Physiol Gastrointest Liver Physiol 2000, 279:G90-G99.
  文献评价指标  
  下载次数:124次 浏览次数:19次