Salem Maha B, El-Lakkany Naglaa M, Hammam Olfat A, Seif El-Din Sayed H
Pharmcology Department, Theodor Bilharz Research Institute, Giza, Egypt.
Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt.
Toxicol Rep. 2024 Dec 16;14:101858. doi: 10.1016/j.toxrep.2024.101858. eCollection 2025 Jun.
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 (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 (10 and 10 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 and 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 (10 CFU) dramatically lowered DAI scores, with the highest Bc dosage (10 CFU) producing the greatest improvement. Furthermore, Bc (10 CFU) substantially ( < 0.05) boosted fecal while decreased , indicating reversal of gut dysbiosis. Bc effectively reduced colonic oxidative stress and inflammation by replenishing GSH and catalase and modulating the NF-κB, Nrf2/HO-1, and TXNIP/NLRP3 pathways. Additionally, Bc (10 CFU) exhibited histologically almost normal mucosa, with maintained architecture and reduced apoptosis, as seen by normalization of Bcl2 and Bax with decreased caspase-3. Collectively, these findings point to the potential usefulness of Bc spores in preventing and treating DSS-induced colitis, positioning them as a promising candidate for UC management.
溃疡性结肠炎（UC）是一种缺乏有效治疗方法的持续性免疫介导疾病，其特征为肠道微生物群失调、NLRP3炎性小体途径异常激活和细胞凋亡。尽管对这些因素的关注日益增加，但了解它们在UC发病机制中的意义仍然是一项挑战。本研究探讨了芽孢杆菌（Bc）孢子在C57BL/6小鼠饮用4%（w/v）葡聚糖硫酸钠（DSS）诱导的小鼠UC模型中的潜在治疗作用。随后，给DSS诱导的小鼠口服不同浓度（10⁸和10⁹菌落形成单位，CFU）的Bc或剂量为200 mg/kg的柳氮磺胺吡啶（SSZ），持续7天。每天利用体重、腹泻和便血等参数计算疾病特异性活动指数（DAI）。研究了粪便中微生物丰度、结肠TXNIP和NLRP3含量以及结肠半胱天冬酶-1、白细胞介素-1β、Bax和Bcl-2表达的变化。此外，还进行了与氧化应激和炎症相关的标志物、组织病理学变化和半胱天冬酶-3免疫组织化学检测。与对照组相比，DSS处理的小鼠DAI评分显著更高，表明患有严重结肠炎。然而，SSZ治疗或Bc（10⁹CFU）显著降低了DAI评分，最高Bc剂量（10⁹CFU）改善最大。此外，Bc（10⁹CFU）显著（P<0.05）增加了粪便中有益菌，同时减少了有害菌，表明肠道菌群失调得到逆转。Bc通过补充谷胱甘肽和过氧化氢酶并调节NF-κB、Nrf2/HO-1和TXNIP/NLRP3途径，有效减轻了结肠氧化应激和炎症。此外，Bc（10⁹CFU）在组织学上显示黏膜几乎正常，结构得以维持，细胞凋亡减少，Bcl2和Bax正常化，半胱天冬酶-3减少。总体而言，这些发现表明Bc孢子在预防和治疗DSS诱导的结肠炎方面具有潜在用途，使其成为UC管理的有希望的候选者。
