Lycopene ameliorates intestinal barrier dysfunction following traumatic brain injury by inhibiting pyroptosis

Traumatic brain injury (TBI) is associated with intestinal barrier dysfunction. Although lycopene (Lyc) possesses anti-inflammatory properties, its specific protective effects against TBI-induced intestinal injury remain unclear. The purpose of this study was to explore the protective effects and mechanisms of Lyc on intestinal injury after TBI. Using a TBI mouse model, mice were divided into CON, TBI, Lyc-L (5 mg/kg/day), Lyc-M (10 mg/kg/day), and Lyc-H (20 mg/kg/day) groups with 14-day continuous treatment. Inflammatory cytokines, intestinal barrier function, and molecular pathways were assessed by enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and western blotting, respectively. A randomized controlled trial enrolled 74 TBI patients, with those in the TBI + Lyc group receiving 300 mL of daily tomato juice (Lyc 30 mg/day) for 14 days, and clinical data collected. In the TBI mouse model, Lyc dose-dependently reduced ileal pro-inflammatory factors (TNF-α, IL-18, IL-6) and enhanced intestinal barrier function—decreasing dysfunction biomarkers (I-FABP, D-LA, DAO, endotoxin) and alleviating pathological damage (lower Chiu score, higher villus height and crypt depth). Moreover, Lyc dose-dependently downregulated the protein expression of NLRP3, ASC, Caspase-1, and GSDMD-N in the ileum post-TBI. In clinical research, Lyc significantly reduced serum CRP and PCT levels, lowered the incidence of gastrointestinal complications, improved intestinal function scores, and increased Glasgow Coma Scale scores. Additionally, it shortened the length of intensive care unit and total hospital stays. Lyc protects against intestinal barrier dysfunction following TBI by suppressing NLRP3/Caspase-1/GSDMD-driven pyroptosis, a mechanism with potential clinical applications.