A curcumin-resveratrol-carnosic acid complex mitigates brain-gut axis disruption in a rodent model of repeated mild traumatic brain injury.

Repetitive mild traumatic brain injury (rmTBI) disrupts the brain-gut axis, contributing to both neurological and gastrointestinal dysfunction. However, interventions targeting this bidirectional pathway remain limited. This study investigates the potential of a bioavailable phytonutrient complex, CGM+, comprising curcumin, trans-resveratrol, and carnosic acid in mitigating rmTBI-induced gut dysbiosis, metabolic imbalance, and intestinal barrier disruption in Sprague-Dawley rats. Animals were randomized into Sham, rmTBI, and CGM+ groups. The CGM+ group received oral supplementation for 21 days, while the others received vehicle. rmTBI was induced on Days 6 and 7 in all groups except Sham. To study the effect of rmTBI on the gut, gut microbiota composition was analyzed via 16 S rRNA sequencing, SCFAs were measured using GC-MS/MS, and intestinal integrity was assessed histologically. Findings demonstrate that CGM+ significantly restored microbial diversity, normalized the abundance of beneficial taxa, and suppressed opportunistic taxa. The predictive functional analysis revealed preservation of SCFA biosynthetic pathways, substantiated by normalized fecal acetate, propionate, and butyrate levels. Histopathological analysis revealed reduced villus atrophy and inflammation, accompanied by increased expression of tight junction proteins ZO-1 and Claudin-1, and decreased Zonulin expression, indicating improved barrier function. These gastrointestinal improvements align with prior evidence of CGM+ driven neurogenesis and cognitive recovery, emphasizes its role in modulating the brain-gut axis. Overall, these findings position CGM + as a promising nutraceutical strategy for managing post-TBI gastrointestinal complications.