emeriitprofessor Marika Mikelsaar (TÜ mikrobioloogia instituut)
professor Eugenia Elefterios Venizelos Bezirtzolou, MD, PhD (Traakia Demokritose Ülikool, Kreeka)
Salmonella enterica serovar Typhi can lead to the development of persistent infection and the formation of granulomas in the liver. Though the prevalence of typhoid fever is low in Estonia, it is still a problem in the developing world. As S. Typhi is restricted to humans, there are no suitable animal models with the particular microbe. In order to study the pathogenesis of typhoid fever, S. Typhimurium has been used in a murine model of systemic infection mimicking persistence observed in S. Typhi carriers. Lactobacillus spp. belongs to normal human microbiota. Probiotic strains belong to the category of organisms classified as generally regarded as safe. Their mode of action is strain-specific: antagonistic influence on pathogens due to the production of hydrogen peroxide, lactic acid, and/or bacteriocins, adhesion, and immunomodulation. The influence and mode of action of probiotic lactobacilli on persistent infections is not known yet. We aimed to detect the effect of lactobacilli of human origin (the probiotic strain Lactobacillus fermentum ME-3 DSM 14241 and Lactobacillus acidophilus E1) on microbiological, histological, biochemical and immunological status of mice in Salmonella Typhimurium persistent infection model, and to detect the impact of the probiotic strain Lactobacillus plantarum Inducia DSM 21379 on the total count of lactobacilli and the immunological response in the gut of mice. For the microbiological detection of Salmonella Typhimurium and lactobacilli, cultures from the blood, liver, spleen, and gut were performed. Histological slides were prepared from the liver, spleen and ileum. The oxidative stress markers: glutathione redox ratio (GSSG/GSH), lipid peroxides (LPO) and Fe content, and concentration of cytokines: INF-γ, TNF-α ja IL-10 in the mucosa of the ileum and liver were estimated. The results of the study indicate that, 1. The elaborated persistent S.Typhimurium infection is characterized by the presence of viable S. Typhimurium in the blood and organs. The presence of granulomas in the liver and spleen is accompanied by increased levels of OxS indices and increased values of TNF-α and INF-γ in the gut and liver. 2. The application of two lactobacilli of human origin, L. fermentum ME-3 with high antimicrobial and antioxidative potential in vitro and L. acidophilus E-1, for 10 days, did not eradicate S.Typhimurium or prevent the developement of granulomas in the liver. An improvement of the gut mucosal barrier was detected due to decreased values of lipid peroxides and glutathione redox ratio of gut mucosa. 3 The intake of cheese containing Lactobacillus plantarum Inducia during one month increased the count of intestinal lactobacilli and hyperplasia of lymphatic follicles in the ileum and colon of healthy mice, indicating a trend of enhancement of the defence capability of intestinal mucosa by probiotic lactobacilli. 4. The combined treatment of ofloxacin and L. fermentum ME-3 increased the eradication of Salmonella Typhimurium, reduced the prevalence of granulomas in the liver, and decreased oxS indices. On Day 10 after inoculation, a reduction of INF-γ in the liver and an increase of IL-10 were detected in the mice without typhoid nodules in the liver. The absence of liver granulomas was associated with a higher total count of lactobacilli in the gut. Thus, in case of antibacterial treatment of persisting Salmonella sp. infection probiotic L. fermentum ME-3 facilitates the eradication of the agent due to its antagonistic, antioxidative and immuunomodulatory activity.