Evaluation of Lacticaseibacillus casei 39 Paraprobiotic in Modulating Inflammatory and Oxidative Pathways in Acetic Acid Induced Ulcerative Colitis

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Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by mucosal inflammation, oxidative stress, and increased apoptosis. This study investigated the therapeutic effects of UV‐C‐inactivated Lacticaseibacillus casei 39 (paraprobiotic) in an acetic acid‐induced UC rat model. The study evaluated its effects on clinical symptoms, inflammatory cytokines, oxidative stress, growth factor expression, PI3K/AKT pathway activation, and apoptotic markers. Paraprobiotic was obtained by UV‐C inactivation of 10 8 CFU/mL L. casei 39. Female Wistar rats were divided into four groups: Control, UC, UC + Probiotic, and UC + Paraprobiotic ( n = 10/group for clinical, ELISA, and oxidative stress analyses; n = 3 pooled/group for Western blot). UC was induced by rectal acetic acid administration, followed by daily oral treatments for 6 days. Clinical signs (DAI, weight change), plasma/tissue cytokines (ELISA, Western blot), oxidative stress (colon TOC/TAC), VEGF/EGF mRNA (qRT‐PCR), and apoptosis/PI3K/AKT pathway proteins (Western blot) were assessed. The UC group showed severe colitis, increased TNF‐α and IL‐6, decreased IL‐10, elevated TOC, reduced TAC, altered VEGF/EGF mRNA, PI3K/AKT activation, and increased apoptosis (Bax/Bcl‐2 ratio, Cytochrome c, Caspase‐9, Caspase‐3). Paraprobiotic treatment improved clinical symptoms, reduced pro‐inflammatory cytokines, and increased anti‐inflammatory cytokines, modulated growth factor expression, reduced oxidative stress, suppressed PI3K/AKT signaling, and downregulated apoptotic markers. TOC decreased 2.10‐fold ( p < 0.01), TAC increased 5.43‐fold ( p < 0.001), and Bax/Bcl‐2 ratio and Caspase‐3 expression were significantly reduced ( p < 0.001 vs. UC; Caspase‐3 also p < 0.05 vs. UC + Probiotic). L. casei 39 paraprobiotic exhibits potent anti‐inflammatory, antioxidant, and anti‐apoptotic effects in UC, suggesting its promise as a novel, multi‐target therapeutic agent.

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