Beneficial microbes that target molecules and pathways, such as oxidative stress, which can negatively affect both host and microbiota, may hold promise as an
inflammatory bowel disease therapy. Prior work showed that a five-strain fermented milk product (
FMP) improved
colitis in T-bet(-/-) Rag2(-/-) mice. By varying the number of strains used in the
FMP, we found that Lactococcus lactis I-1631 was sufficient to ameliorate
colitis. Using comparative genomic analyses, we identified genes unique to L. lactis I-1631 involved in
oxygen respiration. Respiration of
oxygen results in
reactive oxygen species (ROS) generation. Also, ROS are produced at high levels during intestinal
inflammation and cause tissue damage. L. lactis I-1631 possesses genes encoding
enzymes that detoxify ROS, such as
superoxide dismutase (SodA). Thus, we hypothesized that lactococcal SodA played a role in attenuating
colitis. Inactivation of the sodA gene abolished L. lactis I-1631's beneficial effect in the T-bet(-/-) Rag2(-/-) model. Similar effects were obtained in two additional colonic
inflammation models,
Il10(-/-) mice and
dextran sulfate sodium-treated mice. Efforts to understand how a lipophobic
superoxide anion (O2 (-)) can be detoxified by cytoplasmic lactoccocal SodA led to the finding that host antimicrobial-mediated lysis is a prerequisite for SodA release and SodA's extracytoplasmic O2 (-) scavenging. L. lactis I-1631 may represent a promising vehicle to deliver
antioxidant,
colitis-attenuating SodA to the inflamed intestinal mucosa, and host antimicrobials may play a critical role in mediating SodA's bioaccessibility.