Anti-inflammatory Effects of Lactobacillus fermentum ZS40 in a DSS-induced Murine Colitis Model
Zixia Chen
Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China.
Long Yi
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.
Yanni Pan
Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China.
Xingyao Long
Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China.
Jianfei Mu
Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China.
Ruokun Yi *
Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China.
Xin Zhao *
Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China.
*Author to whom correspondence should be addressed.
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a complex aetiology and a potential risk of progression to colon cancer. Probiotics, which are beneficial bacteria naturally residing in the human body, have demonstrated efficacy in modulating gut microbiota balance and mitigating inflammation. This study aimed to investigate the therapeutic effects of Lactobacillus fermentum ZS40 (ZS40) on dextran sulfate sodium (DSS)- induced ulcerative colitis in mice. Disease severity was assessed by measuring colon length and weight and by examining histopathological changes in colon tissues. Furthermore, the impacts of ZS40 on oxidative stress and inflammatory responses were evaluated using biochemical assays, ELISA, real-time quantitative PCR (RT-qPCR), and western blot analysis. The results showed that ZS40 treatment alleviated colonic damage, reducing inflammatory cell infiltration and goblet cell necrosis. It significantly increased the serum levels of total superoxide dismutase (SOD) and catalase (CAT), while decreasing myeloperoxidase (MPO) and malondialdehyde (MDA). ZS40 also modulated the cytokine balance by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory cytokines. Mechanistically, ZS40 downregulated the mRNA and protein expression of nuclear factor-κB p65 (NF-κB p65), IL-6, and TNF-α, while upregulating the expression of inhibitor of kappa B alpha (IκB- α). Additionally, it suppressed the MAPK pathway, evidenced by the downregulated mRNA expression of p38 and JNK1/2, as well as reduced levels of p38, phosphorylated p38 (p-p38), JNK1/2, and phosphorylated JNK1/2 (p-JNK1/2) proteins. In conclusion, our findings suggest that Lactobacillus fermentum ZS40 ameliorates DSS-induced colitis by attenuating oxidative stress and inflammation, potentially through the NF-κB and MAPK signalling pathways, indicating its promise as a therapeutic candidate for ulcerative colitis.
Keywords: Lactobacillus fermentum, dextran sulfate sodium, ulcerative colitis, NF-κB, MAPK