Severity-stratified gut microbiome dysbiosis and systemic neuroinflammation in acute traumatic brain injury: a metagenomic and cytokine profiling study.

Background: The gut-brain axis has increasingly been implicated in the pathophysiology of traumatic brain injury (TBI). However, few human studies have simultaneously examined gut functional metagenomics and peripheral cytokine profiles across mild to moderate-to-severe TBI, which limits our understanding of how gut health may influence recovery outcomes in TBI patients. Methods: This cross-sectional case-control investigation involved the collection of fecal and matched serum samples within 7 days post-injury from 60 mild TBI patients (MT; GCS 13-15), 45 moderate-to-severe TBI patients (MST; GCS ≤ 12), and 113 healthy controls (HC). Shotgun metagenomic sequencing examined gut microbiota. Serum IL-1β, IL-6, IL-8, and TNF-α were measured using a 4-plex Luminex test. Spearman correlation was utilized to construct a hypothesis relating cytokine levels to microbial severity-stratified abundance patterns. Results: TBI was associated with severity-dependent remodeling of the gut microbiota. Alpha diversity decreased from HC to MST ( Conclusion: Acute TBI is associated with severity-specific gut dysbiosis, which is accompanied by systemic neuroinflammation. The early reduction of butyrate-producing taxa in mild TBI suggests that the early post-injury period may represent a potential window for future gut-targeted intervention studies.