The viability of Lactobacillus fermentum CECT5716 is not essential to exert intestinal anti-inflammatory properties.

Probiotics have been used as alternative therapies in intestinal inflammatory disorders. Many studies have shown that different bacterial probiotic strains possess immuno-modulatory and anti-inflammatory properties. However, there is an increasing interest in the use of non-viable bacteria to reduce the risk of microbial translocation and infection. The aim of this study was to evaluate whether the viability of L. fermentum CECT5716 is essential to exert its intestinal anti-inflammatory effect. We compared the preventative effects of viable and non-viable probiotic in the TNBS model of rat colitis. In vitro studies were also performed in Caco-2 and RAW 264.7 cells to evaluate the probiotic effects on IL-8, IL-1β and nitrite production, and p44/42 and p38 MAP kinase protein expressions. In vitro results revealed a decrease in the stimulated production of pro-inflammatory mediators regardless of the viability of the probiotic. Likewise, both forms of the probiotic administered to colitic rats produced a significant reduction of IL-1β and TNF-α levels and colonic iNOS expression. In conclusion, both live and dead L. fermentum CECT5716 have been demonstrated to attenuate the inflammatory process and diminish the production of some of the inflammatory mediators. In fact, the viability of this probiotic did not affect its immuno-modulatory and anti-inflammatory properties.

[1]  V. Péton,et al.  Surface proteins of Propionibacterium freudenreichii are involved in its anti-inflammatory properties. , 2015, Journal of proteomics.

[2]  M. Hibberd,et al.  Enterococcus faecalis from Healthy Infants Modulates Inflammation through MAPK Signaling Pathways , 2014, PloS one.

[3]  Wei-xin Liu,et al.  Heat-killed VSL#3 Ameliorates Dextran Sulfate Sodium (DSS)-Induced Acute Experimental Colitis in Rats , 2013, International journal of molecular sciences.

[4]  R. P. Ross,et al.  Intestinal microbiota, diet and health , 2013, British Journal of Nutrition.

[5]  M. Morowitz,et al.  The intestinal microbiome and necrotizing enterocolitis , 2013, Current opinion in pediatrics.

[6]  H. Ford,et al.  The role of the intestinal microbiota in the pathogenesis of necrotizing enterocolitis , 2013, Seminars in Pediatric Surgery.

[7]  K. Whelan,et al.  Probiotics in the management of irritable bowel syndrome and inflammatory bowel disease , 2013, Current opinion in gastroenterology.

[8]  R. Fedorak,et al.  Probiotic bacteria in the prevention and the treatment of inflammatory bowel disease. , 2012, Gastroenterology clinics of North America.

[9]  M. Hollenberg,et al.  The EGF Receptor and HER2 Participate in TNF-α-Dependent MAPK Activation and IL-8 Secretion in Intestinal Epithelial Cells , 2012, Mediators of inflammation.

[10]  F. Cominelli,et al.  New insights into the dichotomous role of innate cytokines in gut homeostasis and inflammation. , 2012, Cytokine.

[11]  M. Comalada,et al.  The immunomodulatory properties of viable Lactobacillus salivarius ssp. salivarius CECT5713 are not restricted to the large intestine , 2012, European Journal of Nutrition.

[12]  W. D. de Vos,et al.  Intestinal microbiota in human health and disease: the impact of probiotics , 2011, Genes & Nutrition.

[13]  F. Pérez-Cano,et al.  In vitro immunomodulatory activity of Lactobacillus fermentum CECT5716 and Lactobacillus salivarius CECT5713: two probiotic strains isolated from human breast milk. , 2010, Immunobiology.

[14]  M. Gobbetti,et al.  Functional Microorganisms for Functional Food Quality , 2010, Critical reviews in food science and nutrition.

[15]  C. Adams.  The probiotic paradox: live and dead cells are biological response modifiers , 2010, Nutrition Research Reviews.

[16]  A. Dhanani,et al.  Probiotic attributes of Lactobacillus strains isolated from food and of human origin , 2010, British Journal of Nutrition.

[17]  E. Ihara,et al.  Mitogen-Activated Protein Kinase Pathways Contribute to Hypercontractility and Increased Ca2+ Sensitization in Murine Experimental Colitis , 2009, Molecular Pharmacology.

[18]  R. Strieter,et al.  Therapeutic Effect of Blocking CXCR2 on Neutrophil Recruitment and Dextran Sodium Sulfate-Induced Colitis , 2009, Journal of Pharmacology and Experimental Therapeutics.

[19]  T. Hisamatsu,et al.  The nature of floral signals in Arabidopsis. II. Roles for FLOWERING LOCUS T (FT) and gibberellin , 2008, Journal of experimental botany.

[20]  H. Ogata,et al.  Innate immunity in inflammatory bowel disease: state of the art , 2008, Current opinion in gastroenterology.

[21]  R. Kekkonen,et al.  Probiotic Leuconostoc mesenteroides ssp. cremoris and Streptococcus thermophilus induce IL-12 and IFN-gamma production. , 2008, World journal of gastroenterology.

[22]  B. Foligné,et al.  Lactobacillus fermentum ACA-DC 179 displays probiotic potential in vitro and protects against trinitrobenzene sulfonic acid (TNBS)-induced colitis and Salmonella infection in murine models. , 2008, Journal of food microbiology.

[23]  Warren Strober,et al.  The mechanism of action of probiotics , 2007, Current opinion in gastroenterology.

[24]  M. Geier,et al.  Lactobacillus fermentum BR11, a potential new probiotic, alleviates symptoms of colitis induced by dextran sulfate sodium (DSS) in rats. , 2007, International journal of food microbiology.

[25]  M. Comalada,et al.  A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis , 2007, British Journal of Nutrition.

[26]  J. Pennings,et al.  Evaluation of immunomodulation by Lactobacillus casei Shirota: immune function, autoimmunity and gene expression. , 2006, International journal of food microbiology.

[27]  J. Adrio,et al.  Lactobacillus fermentum, a probiotic capable to release glutathione, prevents colonic inflammation in the TNBS model of rat colitis , 2006, International Journal of Colorectal Disease.

[28]  J. Xaus,et al.  Antimicrobial potential of four Lactobacillus strains isolated from breast milk , 2006, Journal of applied microbiology.

[29]  K. A. Malik,et al.  Probiotics and their fermented food products are beneficial for health , 2006, Journal of applied microbiology.

[30]  N. Antille,et al.  Enterococcus faecium SF68 enhances the immune response to Giardia intestinalis in mice. , 2005, The Journal of nutrition.

[31]  M. Comalada,et al.  Preventative Effects of Lactulose in the Trinitrobenzenesulphonic Acid Model of Rat Colitis , 2005, Inflammatory bowel diseases.

[32]  P. Malfertheiner,et al.  Inhibition of p38 MAP kinase‐and RICK/NF‐κB‐signaling suppresses inflammatory bowel disease , 2004 .

[33]  D. Podolsky,et al.  Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. , 2004, Gastroenterology.

[34]  S. Akira,et al.  Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. , 2004, Gastroenterology.

[35]  Penny A. Johnson,et al.  Distribution of the interleukin‐8 receptors, CXCR1 and CXCR2, in inflamed gut tissue , 2000, The Journal of pathology.

[36]  C. Elson,et al.  Experimental models of inflammatory bowel disease. , 1995, Gastroenterology.

[37]  A. Huber,et al.  Regulation of transendothelial neutrophil migration by endogenous interleukin-8. , 1991, Science.

[38]  M. Steinbeck,et al.  Activation of bovine neutrophils by recombinant interferon-γ☆ , 1986 .

[39]  F. Powrie,et al.  Glutathione monoethyl ester: preparation, uptake by tissues, and conversion to glutathione. , 1985, Archives of biochemistry and biophysics.

[40]  M. Comalada,et al.  Prebiotics and Probiotics in Experimental Models of Rodent Colitis: Lessons in Treatment or Prevention of Inflammatory Bowel Diseases , 2010 .

[41]  K. Boockvar,et al.  Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. , 1996, Methods in enzymology.

[42]  M. Steinbeck,et al.  Activation of bovine neutrophils by recombinant interferon-gamma. , 1986, Cellular immunology.

[43]  W. Stenson,et al.  Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. , 1984, Gastroenterology.