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

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Salem M.B.; El-Lakkany N.M.; Hammam O.A.; Seif el-Din S.H.

Journal: Toxicology Reports

Publisher: Elsevier Inc.

Publication Date: June 2025

Volume / Issue: Volume 14

Article No.: 101858

ISSN: 22147500

DOI: 10.1016/j.toxrep.2024.101858

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Salem M.B., Pharmcology Department, Theodor Bilharz Research Institute, Giza, Egypt; El-Lakkany N.M., Pharmcology Department, Theodor Bilharz Research Institute, Giza, Egypt; Hammam O.A., Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt; Seif el-Din S.H., Pharmcology Department, Theodor Bilharz Research Institute, Giza, Egypt

Abstract

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 < 0.05) boosted fecal Firmicutes while decreased Bacteroidetes, 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 (1010 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. © 2024 The Authors

Keywords

Apoptosis; Bacillus clausii; Bacteroidetes; Firmicutes; Inflammasome pathway; Ulcerative colitis; caspase 3; catalase; cryopyrin; dextran sulfate; glutathione; heme oxygenase 1; interleukin 1beta; interleukin 1beta converting enzyme; malonaldehyde; nitric oxide; protein Bax; protein bcl 2; salazosulfapyridine; thiopental; thioredoxin interacting protein; transcription factor Nrf2; animal experiment; animal model; animal tissue; Article; bacterial spore; body weight; colony forming unit; controlled study; diarrhea; disease activity; dysbiosis; enzyme linked immunosorbent assay; gene expression; hematochezia; histopathology; homeostasis; immunohistochemistry; inflammation; intestine flora; male; mouse; NF kB signaling; nonhuman; oxidative stress; real time polymerase chain reaction; RNA extraction

Citation Information

Scopus Citations: 11

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