Gut microbiome remodeling by antibiotics reduces neuroinflammation in traumatic brain injury

Traumatic brain injury (TBI) induces both neuroinflammation and gut microbiome dysbiosis, yet the influence of antibiotics (ABX) on TBI-related neuropathology remains unclear. We administered a broad-spectrum oral ABX regimen to deplete the gut microbiome in single and repeated TBI mouse models. In male mice, ABX treatment significantly reduced neuroinflammation and neurodegeneration post-TBI, with no effects observed in uninjured controls. ABX also altered microbiome composition and decreased serum and fecal short-chain fatty acid levels, while intestinal damage and dysbiosis were further exacerbated by TBI severity. Notably, germ-free male mice exhibited heightened neuroinflammation and larger lesion volumes following TBI, underscoring the microbiome’s essential role in recovery. Metagenomic analyses revealed Parasutterella excrementihominis and Lactobacillus johnsonii as potential ABX-resistant taxa post-injury. These findings suggest that short-term ABX treatment may attenuate TBI-induced neuroinflammation by reshaping the gut microbiome, offering directions for microbiome-targeted therapies in TBI.