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Probiotics alleviate inflammatory bowel disease in mice by regulating intestinal microorganisms-bile acid-NLRP3
11Department of Internal Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China; 2Department of Internal Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
Abstract:
The objective of the present study was to elucidate the mechanism of intestinal microorganisms- bile acid- NLRP3 inflammasome regulation in mice with inflammatory bowel disease treated with probiotics. The abnormal activation of NLRP3 inflammasome is the main pathogenic factor that leads to the development of chronic colitis in IL-10-/- mice. In this study, we divided the IL-10-/- and wild-type mice on a C57BL/6 background into 3 groups: control group (wt mice, n=10), IBD group (IL-10-/- mice, n=10), and probiotic group (IL-10-/- mice treated with probiotics, n=10). The analyses included mRNA levels of cytokines and protein expression of NLRP3 inflammasome and NOD2, as well as colorimetric determination of Wnt, Notch and BMP activity in colon tissue and fresh colon mass. The fresh colon mass was increased in the IBD mice when compared with the control and the probiotic groups (P<0.05). The histological score of the proximal colon in the IBD group was higher than in two other groups (P<0.05). The probiotic group showed lower levels of IFN-γ, IL-17F, IL-1α and IL-25 mRNA compared to the IBD group (P<0.05). The main components of NLRP3 inflammasome (NLRP3, ASC, caspase-1 and IL-1β) and NOD2 were increased in IBD group compared to the control, and decreased after probiotic treatment (P<0.05). FXR, TGR5, vitamin D, and CAR were all increased in IBD group compared to the control and probiotic groups (P<0.05). In conclusion, probiotics modulated the intestinal microbial-bile acid-NLRP3 inflammation in IBD mice.
Insights
Probiotics regulate gut microbiota-bile acid-NLRP3 inflammasome pathways in mice with inflammatory bowel disease (IBD). This study shows probiotics reduce inflammation and improve colon health in IBD models.
Area of Science:
- Gastroenterology and Immunology
- Microbiome Research
- Inflammation Biology
Background:
- Abnormal activation of the NLRP3 inflammasome is a key factor in chronic colitis development in IL-10 knockout mice.
- Understanding the interplay between intestinal microorganisms, bile acids, and the NLRP3 inflammasome is crucial for IBD pathogenesis.
Purpose of the Study:
- To elucidate the regulatory mechanism of intestinal microorganisms-bile acid-NLRP3 inflammasome in probiotic-treated inflammatory bowel disease (IBD) mice.
- To investigate the therapeutic effects of probiotics on chronic colitis in IL-10-/- mice.
Main Methods:
- Comparison of control (wild-type), IBD (IL-10-/-), and probiotic-treated (IL-10-/-) mice.
- Analysis of cytokine mRNA levels, NLRP3 inflammasome and NOD2 protein expression.
- Colorimetric determination of Wnt, Notch, BMP, FXR, TGR5, vitamin D, and CAR activity in colon tissue.
Main Results:
- IBD mice exhibited increased colon mass and histological scores, which were reduced by probiotic treatment.
- Probiotics decreased mRNA levels of IFN-γ, IL-17F, IL-1α, and IL-25.
- NLRP3 inflammasome components (NLRP3, ASC, caspase-1, IL-1β) and NOD2 were elevated in IBD mice and reduced by probiotics.
Conclusions:
- Probiotics effectively modulate the intestinal microbial-bile acid-NLRP3 inflammasome axis in a mouse model of IBD.
- Probiotic intervention ameliorates inflammation and improves colon tissue integrity in chronic colitis.
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