Effects of paraprobiotic Lactobacillus acidophilus LA ‐5 on PANoptosis , oxidative stress and inflammation in acetic acid‐induced ulcerative colitis

BACKGROUND Ulcerative colitis (UC) is a relapsing inflammatory bowel disease characterised by oxidative stress, inflammation and regulated cell death of the colonic mucosa. Because live probiotics may cause bacteraemia and sepsis in immunocompromised hosts, non‐viable (paraprobiotic) alternatives have attracted interest. METHODS This study evaluated the antioxidant, anti‐inflammatory and PANoptosis‐regulating effects of a heat‐inactivated paraprobiotic derived from Lactobacillus acidophilus LA‐5 in acetic acid (AA)‐induced experimental UC, compared to the live probiotic. Forty female Balb/c mice were assigned to four groups ( n = 10): healthy control, AA colitis, live LA‐5 (AA‐PRO) and heat‐inactivated paraprobiotic (AA‐PARA). Colitis was induced by intrarectal administration of 4% acetic acid, and treatments were given by oral gavage for 7 days. Disease activity, colon histopathology, oxidant/antioxidant biomarkers, serum cytokines, PANoptosis‐related proteins (western blot) and caecal short‐chain fatty acids were assessed. RESULTS AA increased the disease activity index, shortened the colon and induced splenomegaly, histopathological damage, oxidative stress and a systemic cytokine surge. Both treatments limited these changes; the paraprobiotic preserved colon length, reversed splenomegaly and regulated interleukin (IL)‐6/IL‐10 more effectively than the live probiotic ( P < 0.05). All elevated PANoptosis markers (NLRP3, c‐GSDMD, c‐IL‐1 β , p‐RIPK3, p‐MLKL, c‐caspase‐3, c‐GSDME and ZBP1) were suppressed by both treatments. ZBP1 was suppressed significantly more by the paraprobiotic ( P < 0.05), which also increased butyric and valeric acid. CONCLUSION The L. acidophilus LA‐5 paraprobiotic exerts protective effects at least equivalent to the live probiotic, supporting its potential as a safe therapeutic candidate for UC.