IDDF2023-ABS-0313 Clostridium butyricum alleviates DSS-induced colitis mice by inhibiting NLRP3 inflammasome activation

Background

Clostridium butyricum (CB) is a butyric acid-producing bacterium that is thought to exert a probiotic effect in IBD. NLRP3 inflammasomes are an important component of intrinsic immunity, but the role of NLRP3 inflammasome activation is currently controversial. This study aims to investigate the role and mechanisms of CB on dextran sodium sulfate (DSS)-induced NLRP3 inflammasome activation in colitis.

Methods

Fourty-eight 6-8 week old C57BL/6 wild-type mice (WT) and matched NLRP3 knockout mice (KO) were randomly divided into six groups, and Clostridium butyricum MIYAIRI 588 was used to treat colitis mice. The body weight, disease activity index (DAI), and colon length of mice were observed, respectively. The relative expression of inflammatory pathways of NLRP3 in colon tissue was detected by qRT-PCR, and HE staining, IHC, and AB-PAS staining were shown.

Results

In WT groups, after CBM intervention, the degree of weight loss was alleviated (IDDF2023-ABS-0313 Figure 1A. Relative weight change of mice during the experimental treatment), the shortened colon length was improved (IDDF2023-ABS-0313 Figure 1B-C. The general appearance of the colon of mice in each group and the colon length), the DAI of mice was decreased (IDDF2023-ABS-0313 Figure 1D. Disease activity index (DAI) dynamics across each group), NLRP3 and IL-1β levels of expression were decreased (IDDF2023-ABS-0313 Figure 1E-F. NLRP3 and IL-1β expression measured by qRT-PCR) and colonic pathological staining, IHC and AB-PAS staining in mice were improved significantly (IDDF2023-ABS-0313 Figure 1G-H. Colonic tissues stained with H&E, IHC, and AB-PAS staining (200×, 400×) and IHC score). In the KO group, significant relief of symptoms in the DSS group, but no significant difference between the DSS group and CBM group.

Conclusions

CBM alleviates DSS-induced colitis by inhibiting NLRP3 inflammation activation, which may be another potential mechanism of action in the treatment of IBD.