Bacillus clausii spores maintain gut homeostasis in murine ulcerative colitis via modulating microbiota, apoptosis, and the TXNIP/NLRP3 inflammasome cascade

• Published in: Toxicology reports 2025-06, Vol.14, p.101858, Article 101858
• Main Authors: Salem, Maha B., El-Lakkany, Naglaa M., Hammam, Olfat A., Seif el-Din, Sayed H.
• Format: Article
• Language: English
• Subjects: Apoptosis; Bacillus clausii; Bacteroidetes; Firmicutes; Inflammasome pathway; Ulcerative colitis
• ISSN: 2214-7500; 2214-7500
• DOI: 10.1016/j.toxrep.2024.101858

Ulcerative colitis (UC), a persistent immune-mediated disorder lacking effective treatment, is distinguished by gut microbiota dysbiosis, abnormal activation of the NLRP3 inflammasome pathway, and apoptosis. Despite growing attention to these factors, understanding their significance in UC pathogenesis remains a challenge. The present study explores the potential therapeutic impact of Bacillus clausii (Bc) spores in a murine UC model induced by drinking 4 % (w/v) dextran sulfate sodium (DSS) in C57BL/6 mice. Subsequently, the DSS-induced mice were orally administered either Bc at varying concentrations (105 and 1010 Colony forming unit, CFU) or sulfasalazine (SSZ) at a dosage of 200 mg/kg for 7 days. The disease-specific activity index (DAI) was calculated daily utilizing parameters such as body weight, diarrhea, and bloody stool. Changes in fecal Firmicutes and Bacteroidetes abundance, colonic TXNIP and NLRP3 contents, as well as colonic caspase-1, IL-1β, Bax, and Bcl-2 expression, were investigated. Additionally, markers related to oxidative stress and inflammation, histopathological changes and caspase-3 immunohistochemistry testing were conducted. DSS-treated mice had significantly higher DAI scores compared to controls, indicating severe colitis. However, SSZ treatment or Bc (105 CFU) dramatically lowered DAI scores, with the highest Bc dosage (1010 CFU) producing the greatest improvement. Furthermore, Bc (1010 CFU) substantially (p