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

Many probiotic bacteria have been described as a promising tool in the therapy of Inflammatory Bowel Diseases (IBD). Most of them belong to the Lactic Acid Bacteria (LAB) group, which makes part of our healthy microbiota. However, little is known about the effects of transiting dairy bacteria that make part of our diet, including Lactococcus lactis. In the present study, we analyzed the immune modulation effects of three L. lactis strains in vitro using intestinal epithelial cells and the effectiveness of a selected strain in a murine model of colitis. Only one strain, L. lactis NCDO 2118, was able to reduce the IL1-β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect of this strain. In vivo, L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during a remission period between a first and second course of colitis induced by dextran sulfate sodium. This resulted in a milder form of recurrent colitis than observed in mice administered medium during this same period. This protective effect was not attributable to changes in secretory IgA, however NCDO 2118 administration was associated with early increase in IL-6 production and by the maintenance of IL-10 in colonic tissue. Mice fed with L. lactis NCDO 2118 increased the number of regulatory CD4+ T cells bearing surface TGF-β in the form of latency-associated protein in mesenteric lymph node and spleen. The results of this study allowed us to identify a new probiotic strain that may be used in the treatment of IBD as well as some of the mechanism involved in its anti-inflammatory effect. Fil: Diniz Luerce, Tessália. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Gomes Santos, Ana Cristina. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Santos Rochat, Clarissa. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Garcias Moreira, Thais. Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciência de Alimentos.; BrasilFil: Nogueira Cruz, Déborah. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Lemos, Luísa. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Sousa, Adna Luciana. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Bastos Pereira, Vanessa. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: de Azevedo, Marcela. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Moraes, Kátia. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Carmona Cara, Denise. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia; BrasilFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Azevedo, Vasco. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Caetano Faria, Ana Maria. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Miyoshi, Anderson. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; Brasi

Oral administration of Lactococcus lactis expressing recombinant 15-lipoxygenase-1 (15 LOX-1) modulates chemically induced colitis in mice

Background: Inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, are characterized by extensive inflammation due to dysregulation of the innate and adaptive immune system whose exact etiology is not yet completely understood. Currently there is no cure for IBD, thus the search for new molecules capable of controlling IBD and their delivery to the site of inflammation are the goal of many researchers. The aim of this work was to evaluate the anti-inflammatory effect of the oral administration of a Lactococcus (L.) lactis strain producing 15-lipoxygenase-1 (15-LOX-1) using a dextran sodium sulfate (DSS)-induced IBD mouse model. Methods: The anti-inflammatory strain L. lactislacti NCDO 2118 was modified to produce active 15-LOX-1 and tested in in a DSS induced IBD mouse model. Results: This 15-LOX-1 producing L. lactis was effective in the prevention of the intestinal damage associated to inflammatory bowel disease in a murine model and decreased pro-inflammatory cytokines such as IFN-γ and IL-4 while increasing the anti-inflammatory cytokine IL-10. L. lactis NCDO 2118 acts not just as a tool to delivery 15-LOX-1 in the inflamed gut mucosa but still retains its anti-inflammatory effects. Conclusions: This strain could be used in novel adjunct IBD treatment protocols.Fil: Carvalho, Rodrigo. Universidade Federal do Minas Gerais; BrasilFil: Morais, Kátia. Universidade Federal do Minas Gerais; BrasilFil: Bastos Pereira, Vanessa. Universidade Federal do Minas Gerais; BrasilFil: Gomes Santos, Ana Cristina. Universidade Federal do Minas Gerais; BrasilFil: Diniz Luerce, Tessalia. Universidade Federal do Minas Gerais; BrasilFil: de Azevedo, Marcela. Universidade Federal do Minas Gerais; BrasilFil: Santos Rochat, Clarissa. Universidade Federal do Minas Gerais; BrasilFil: Severiano de Sousa, Cassiana. Universidade Federal do Minas Gerais; BrasilFil: Prósperi, Camila. Universidade Federal do Minas Gerais; BrasilFil: Carmona Cara, Denise. Universidade Federal do Minas Gerais; BrasilFil: Caetano Faria, Ana María. Universidade Federal do Minas Gerais; BrasilFil: Bermudez-Humaran, Luis. Institut National de la Recherche Agronomique; FranciaFil: Blottiere, Hervé. Institut National de la Recherche Agronomique; FranciaFil: Langella, Philippe. Institut National de la Recherche Agronomique; FranciaFil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Pereira Figueiredo, Henrique Cesar. Universidade Federal do Minas Gerais; BrasilFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Miyoshi, Anderson. Universidade Federal do Minas Gerais; BrasilFil: Azevedo, Vasco. Universidade Federal do Minas Gerais; Brasi