Abstract
Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease (IBD) characterized by superficial mucosal inflammation, rectal bleeding, diarrhea, and abdominal pain. Anti-inflammatory and immunosuppressive drugs have been used in the therapy of human UC. Interleukin (IL)-35, which functions as an anti-inflammatory cytokine, has been shown to play a potential therapeutic role in a UC-like mouse colitis induced by dextran sodium sulfate (DSS). However, the contribution of IL-35 via oral administration to colitis prevention has not been determined. In order to explore its preventative potentiality, a dairy Lactococcus lactis NZ9000 strain was engineered to express murine IL-35 (NZ9000/IL-35), and this recombinant bacteria was applied to prevent and limit the development of DSS-induced mouse colitis. We found that oral administration of NZ9000/IL-35 induced the accumulation of IL-35 in the gut lumen of normal mice. When administrated preventatively, NZ9000/IL-35-gavaged mice exhibited decreased weight loss, DAI score, colon shortening as well as colitis-associated histopathological changes in colon, indicating that the oral administration of NZ9000/35 contributed to the suppression of DSS-induced colitis progression. Moreover, much less Th17 cells and higher level of Treg cells in lamina propria, as well as increased colon and serum levels of IL-10 with a concomitant reduced pro-inflammatory cytokines, IL-6, IL-17A, IFN-γ, and TNF-α were apparently regulated by NZ9000/IL-35 in colitis mice. Together, we put forward direct evidence pinpointing the effectiveness of NZ9000/IL-35 in preventing UC-like mouse colitis, implying a potential candidate of this recombinant Lactococcus lactis that prevent the progression of IBD.
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The authors thank Jian Hu for help with histopathological analysis.
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This work was supported by grants from the Program of Science and Technology Development Plan of Jilin Province of China (Grant number, 20170101028JC).
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Fengqi Hao conceived and designed study. Jianyong Wang and Miaomiao Tian performed research; Jianyong Wang and Wei Li analyzed data and wrote the manuscript; Fengqi Hao and Miaomiao Tian contributed to manuscript revision.
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Wang, J., Tian, M., Li, W. et al. Preventative delivery of IL-35 by Lactococcus lactis ameliorates DSS-induced colitis in mice. Appl Microbiol Biotechnol 103, 7931–7941 (2019). https://doi.org/10.1007/s00253-019-10094-9
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DOI: https://doi.org/10.1007/s00253-019-10094-9