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Am J Physiol Gastrointest Liver Physiol 293: G729-G738, 2007. First published July 19, 2007; doi:10.1152/ajpgi.00132.2007
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INFLAMMATION/IMMUNITY/MEDIATORS

Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis

Ian M. Carroll,1 Jason M. Andrus,2 José M. Bruno-Bárcena,3,4 Todd R. Klaenhammer,5 Hosni M. Hassan,4 and Deborah S. Threadgill1

1Department of Genetics, CB 7264, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; 2Department of Biology, Augusta State University, Augusta, Georgia; 3Biomanufacturing Training and Education Center, CB 7928, North Carolina State University, Raleigh, North Carolina; 4Department of Microbiology, North Carolina State University, CB 7615, Raleigh, North Carolina; 5Department of Food Science, North Carolina State University, CB 7624, Raleigh, North Carolina

Submitted 20 March 2007 ; accepted in final form 16 July 2007

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 IL-10-deficient mice were left untreated or supplemented with native L. gasseri or L. gasseri expressing MnSOD for 4 wk. 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 3 days. L. gasseri producing MnSOD significantly reduced inflammation in IL-10-deficient mice compared with untreated controls (P < 0.05), whereas the anti-inflammatory effects of both native and MnSOD producing L. gasseri were more pronounced in males. The anti-inflammatory effects of 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 IL-10-deficient mice. This study demonstrates that L. gasseri producing MnSOD has significant anti-inflammatory activity that reduces the severity of colitis in the IL-10-deficient mouse.

probiotic; Lactobacilli; oxidative stress; inflammatory bowel disease



Address for reprint requests and other correspondence: D. S. Threadgill, Dept. of Genetics, CB7264, Univ. of North Carolina, Chapel Hill, NC 27599 (e-mail: deborah_threadgill{at}med.unc.edu)




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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
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Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G353 - G353.
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