Genetically engineered immunomodulatory Streptococcus thermophilus producing antioxidant enzymes show enhanced anti-inflammatory activities

S. DEL CARMEN; A. DE MORENO DE LEBLANC; R. MARTIN; F. CHAIN; P. LANGELLA; L. BERMUDEZ-HUMARAN; J.G. LEBLANC

APPLIED AND ENVIRONMENTAL MICROBIOLOGY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2014 vol. 80 p. 869 - 877

0099-2240

The aim of this study was to develop lactic acid bacteria (LAB) strains having both immunomodulatory and antioxidant properties and evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus bulgaricus and Streptococcus thermophilus strains were co-cultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after co-incubation with candidate bacteria revealed that L. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profile in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profile in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding for catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight lost, lower liver microbial translocation, lower macroscopic and microscopic damage scores and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (eg. S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an anti-oxidant enzyme enhances its anti-inflammatory activities.