Abstract
Background
Bacillus clausii (B. clausii) is a Gram-positive, spore-forming probiotic widely used for the prevention and treatment of gastrointestinal disorders and may have protective effects against chemotherapy-induced intestinal mucositis. Cyclophosphamide (CP) can induce immunosuppression and intestinal mucosal injury, leading to inflammation and alterations in intestinal homeostasis. This study evaluated the protective effects of B. clausii on intestinal histopathology, inflammation, pro-inflammatory cytokines, and miR-146a expression in a rat model of CP-induced immunosuppression and intestinal mucositis.Methods and results
Thirty-two male Wistar albino rats were randomly allocated into four groups: Group 1 (Control), Group 2 (CP + saline), Group 3 (saline + B. clausii), and Group 4 (CP + B. clausii). Immunosuppression and intestinal mucositis were induced by intraperitoneal CP administration, followed by oral B. clausii treatment. Clinical findings, hematological parameters, histopathology, histomorphometry, cytokine levels, and gene expression were assessed. CP administration impaired body weight gain, altered stool consistency, reduced leukocyte and lymphocyte counts, and caused intestinal mucosal injury with villus shortening, epithelial disruption, inflammatory infiltration, fibrosis, and goblet cell depletion. Villus length decreased by 10.58% and goblet cell count by 44.20% in Group 2 compared with Group 1 (P Conclusions
B. clausii partially attenuated cyclophosphamide-induced intestinal mucositis by improving clinical and histopathological findings, preserving intestinal morphology, restoring goblet cell numbers, and reducing TNF-α and IL-6 levels. The partial recovery of leukocyte and lymphocyte counts suggests potential immunomodulatory effects. Although miR-146a expression was reduced in CP-treated groups, the mechanisms underlying the protective effects of B. clausii remain unclear. Overall, B. clausii may represent a promising supportive probiotic approach for mitigating chemotherapy-induced intestinal mucosal injury. Further mechanistic and clinical studies are warranted to clarify its effects on miR-146a, the intestinal microbiota, inflammatory pathways, and intestinal barrier function.