Milk Fermented with a 15-Lipoxygenase-1-Producing Lactococcus Lactis Alleviates Symptoms of colitis in a Murine Model

Abstract

Inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, is 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 administration of milks fermented by a Lactococcus (L.) lactis strain producing 15-lipoxygenase-1 (15-LOX-1) using a trinitrobenzenesulfonic acid-induced IBD mouse model. The results obtained demonstrated that 15-LOX-1 producing L. lactis was effective in the prevention of the intestinal damage associated to inflammatory bowel disease in a murine model. The work also confirmed previous studies showing that fermented milk is an effective form of administration of recombinant lactic acid bacteria expressing beneficial molecules.

New insights into therapeutic strategies for gut microbiota modulation in inflammatory diseases

“…53 Positive results have been obtained in animal models and human clinical trials using probiotics, especially using recombinant lactic acid bacteria expressing beneficial molecules as a live system delivered to inflammatory sites. [54][55][56][57] The anti-inflammatory effects of the Lactococcus lactis strain, which produces 15-lipoxygenase-1, were shown to be effective in preventing intestinal damage and in alleviating trinitrobenzenesulfonic acid-induced colitis in an experimental murine model. 57 In addition, genetically modified L. lactis expressing cytokines, such as human interleukin-10 (IL-10), has been shown to prevent intestinal damage in experimental colitis.…”

Secretion of biologically active pancreatitis-associated protein I (PAP) by genetically modified dairy Lactococcus lactis NZ9000 in the prevention of intestinal mucositis

“…The use of recombinant LAB strains, such as the model Lactococus lactis for delivering biologically active molecules with anti-inflammatory properties has also been explored as an alternative therapy for the treatment of mucositis and other gastrointestinal inflammatory disorders, as inflammatory bowel diseases (IBD) [ 20 – 23 ]. In 2006, a biological confinement strategy to contain the dissemination of genetically engineered L. lactis strain expressing IL-10 was carried out in phase I clinical trial with IBD patients, suggesting the feasibility of mucosal therapy using recombinant lactococci [ 24 ].…”

Vector Development Timeline for Mucosal Vaccination and Treatment of Disease Using Lactococcus lactis and Design Approaches of Next Generation Food Grade Plasmids

“…Concerning the XIES system, some therapeutic molecules such as 15-lipoxygenase were cloned in it. L. lactis (pXIES:CYT: 15lox-1 )-fermented milk was effective in the prevention of intestinal damage associated with inflammatory bowel disease (IBD) in a trinitrobenzenesulfonic acid-induced IBD mouse model ( Saraiva et al, 2015 ) and, in addition, a decrease in IFN-γ and IL-4 was also observed. Also, an increase in IL-10 was observed in a dextran sodium sulfate-induced (DSS-induced) IBD mouse model, where mice were orally administrated with the culture of this strain ( Carvalho et al, 2016 ).…”