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-1β, 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. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.