Sunflower oil-loaded lycopene protects intestinal barrier integrity following traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of morbidity, mortality, and long-term neurological impairment. Growing evidence suggests that the gut-brain axis plays a crucial role in TBI pathophysiology, with gut microbiota dysbiosis potentially inducing inflammation and aggravating brain injury. Lycopene (Lyc), a potent antioxidant derived from tomatoes with neuroprotective and anti-inflammatory properties, is considered a promising potential therapy for TBI. Sunflower oil (SO) can effectively enhance Lyc bioavailability. We established a TBI mouse model and treated it with SO-loaded Lyc (SO-Lyc). Serum and fecal samples were collected for metabolomic analysis, 16S rRNA sequencing for gut microbiota changes, ELISA for inflammatory cytokines and injury markers, H&E staining for gut/brain histopathology, and immunohistochemistry for intestinal barrier-related gene expression. Furthermore, we used 16S rRNA data from patient samples with TBI to perform association analyses. The results showed that SO-Lyc supplementation may mitigate damage to intestinal and cerebral tissues by restoring intestinal barrier function and suppressing systemic inflammation through modulation of key metabolic pathways, such as those involving linoleic acid, sphingolipids, and tryptophan. Its effects manifest as reduced serum inflammatory cytokines (TNF-α, IL-6, CRP, IL-1β), intestinal injury markers (DAO, D-LA, I-FABP, ET), and brain injury markers (NFL, GFAP, S100B, NSE, UCH-L1), while enhancing the expression of intestinal barrier genes (occludin and ZO-1). Furthermore, this supplement promotes the growth of gut microbiota with anti-inflammatory properties. Differences in inflammation and gut microbiota have been observed among TBI patients with varying degrees of severity, suggesting that Lyc containing SO may be an effective treatment for TBI patients.