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      Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis

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          Abstract

          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.

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          Most cited references39

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          Clinicopathologic study of dextran sulfate sodium experimental murine colitis.

          We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis. Acute colitis was induced in Swiss-Webster mice by 7 days of oral DSS with animals sacrificed daily. Chronic colitis was induced by: (a) 7 days of oral DSS followed by 7 days of H2O (for 1, 2, and 3 cycles) and (b) 7 days of oral DSS followed by 14 and 21 days of H2O. In each experimental group, the entire colons were examined histologically and correlated with clinical symptoms. Acute clinical symptoms (diarrhea and/or grossly bloody stool) were associated with the presence of erosions and inflammation. More importantly, the earliest histologic changes which predated clinical colitis was loss of the basal one-third of the crypt (day 3), which progressed with time to loss of the entire crypt resulting in erosions on day 5. The earliest changes were very focal and not associated with inflammation. Inflammation was a secondary phenomena and only became significant after erosions appeared. Animals treated with only 7 days of DSS followed by 14 and 21 days of H2O developed a chronic colitis with the following histologic features: areas of activity (erosions and inflammation), inactivity, crypt distortion, florid epithelial proliferation and possible dysplasia. These changes were similar to animals given 3 cycles of DSS. The clinical disease activity index correlated significantly with pathologic changes in both the acute and chronic phases of the disease. The mechanism of DSS colitis is presently unknown. However, the finding of crypt loss without proceeding or accompanying inflammation suggests that the initial insult is at the level of the epithelial cell with inflammation being a secondary phenomena. This may be a good model to study how early mucosal changes lead to inflammation and the biology of the colonic enterocyte. Chronic colitis induced after only 7 days of DSS may serve as a useful model to study the effects of pharmacologic agents in human inflammatory disease and mechanisms of perpetuation of inflammation. Finally, we believe that this model has the potential to study the dysplasia cancer sequence in inflammatory disease.
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            Probiotic bacteria enhance murine and human intestinal epithelial barrier function.

            The probiotic compound, VSL#3, is efficacious as maintenance therapy in pouchitis and ulcerative colitis. The aim of this study was to determine the efficacy of VSL#3 as a primary therapy in the treatment of colitis in the interleukin (IL)-10 gene-deficient mouse. Mechanisms of action of VSL#3 were investigated in T(84) monolayers. IL-10 gene-deficient and control mice received 2.8 x 10(8) colony-forming units per day of VSL#3 for 4 weeks. Colons were removed and analyzed for cytokine production, epithelial barrier function, and inflammation. VSL#3 or conditioned media was applied directly to T(84) monolayers. Treatment of IL-10 gene-deficient mice with VSL#3 resulted in normalization of colonic physiologic function and barrier integrity in conjunction with a reduction in mucosal secretion of tumor necrosis factor alpha and interferon gamma and an improvement in histologic disease. In vitro studies showed that epithelial barrier function and resistance to Salmonella invasion could be enhanced by exposure to a proteinaceous soluble factor secreted by the bacteria found in the VSL#3 compound. Oral administration of VSL#3 was effective as primary therapy in IL-10 gene-deficient mice, and had a direct effect on epithelial barrier function.
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              Dendritic cells in intestinal immune regulation.

              A breakdown in intestinal homeostasis can result in chronic inflammatory diseases of the gut including inflammatory bowel disease, coeliac disease and allergy. Dendritic cells, through their ability to orchestrate protective immunity and immune tolerance in the host, have a key role in shaping the intestinal immune response. The mechanisms through which dendritic cells can respond to environmental cues in the intestine and select appropriate immune responses have until recently been poorly understood. Here, we review recent work that is beginning to identify factors responsible for intestinal conditioning of dendritic-cell function and the subsequent decision between tolerance and immunity in the intestine.
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                Author and article information

                Contributors
                Journal
                Gut Pathog
                Gut Pathog
                Gut Pathogens
                BioMed Central
                1757-4749
                2014
                29 July 2014
                : 6
                : 33
                Affiliations
                [1 ]Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 – 31270-901 Belo Horizonte, MG, Brazil
                [2 ]Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
                [3 ]Departamento de Ciência de Alimentos, Faculdade de Farmácia, Belo Horizonte, MG, Brazil
                [4 ]Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
                [5 ]Centro de Referencia para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Argentina
                Article
                1757-4749-6-33
                10.1186/1757-4749-6-33
                4126083
                25110521
                bbfdfb6c-c21b-4a11-a72e-6dd65bee1acc
                Copyright © 2014 Luerce et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 May 2014
                : 20 July 2014
                Categories
                Research

                Gastroenterology & Hepatology
                lactococcus lactis,colitis,cytokines,regulatory t cells,probiotics
                Gastroenterology & Hepatology
                lactococcus lactis, colitis, cytokines, regulatory t cells, probiotics

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