Submitted on March 20, 2007
Accepted on July 16, 2007
The Anti-inflammatory Properties of Lactobacillus gasseri Expressing Manganese Superoxide Dismutase (MnSOD) Using the Interleukin 10-Deficient Mouse Model of Colitis
Ian Michael Carroll1, Jason M Andrus2, Jose M Bruno-Barcena3, Todd R. Klaenhammer4, Hosni M Hassan5, and Deborah S Threadgill1*
1 Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
2 Biology, Augusta State University, Augusta, Georgia, United States
3 Biomanufacturing Training & Education Center (BTEC), North Carolina State University, Raleigh, North Carolina, United States; Microbiology, North Carolina State University, Raleigh, North Carolina, United States
4 Department of Food Science, North Carolina State University, North Carolina, United States; North Carolina State University
5 Microbiology, North Carolina State University, Raleigh, North Carolina, United States
* To whom correspondence should be addressed. E-mail: Deborah_Threadgill{at}med.unc.edu.
Emerging evidence has implicated reactive oxygen species (ROS) in the pathogenesis of inflammatory bowel disease (IBD). Although intestinal epithelial cells produce the ROS-neutralizing enzyme superoxide dismutase (SOD) the protein and activity levels of Copper/Zinc (Cu/Zn) and manganese (Mn) SOD are perturbed in inflamed tissues of IBD patients. Thus, we investigated the ability of MnSOD from Streptococcus thermophilus to reduce colitis symptoms in Interleukin (Il) 10-deficient mice using Lactobacillus gasseri as a delivery vehicle. Cohorts of 13-15 Il10-deficient mice were left untreated or supplemented with native L. gasseri or L. gasseri expressing MnSOD for four weeks. Colonic tissue was collected and inflammation was histologically scored. The presence of innate immune cells was investigated by immunohistochemistry and the host antioxidant response was determined by quantitative PCR. It was demonstrated that L. gasseri was stably maintained in mice for at least three days. L. gasseri producing MnSOD significantly reduced inflammation in Il10-deficient mice compared to untreated controls (P < 0.05), while the anti-inflammatory effects of both native and MnSOD producing L. gasseri were more pronounced in males. The anti-inflammatory effects of the L. gasseri were associated with a reduction in the infiltration of neutrophils and macrophages. Transcripts of antioxidant genes were equivalent in colonic tissues obtained from control and probiotic-treated Il10-deficient mice. This study demonstrates that L. gasseri producing MnSOD has significant anti-inflammatory activity that reduces the severity of colitis in the Il10-deficient mouse.
