Microbiome-Modified Metabolites Predict Acute Brain Injury Outcome

BACKGROUND Acute brain injury (ABI)-mediated disruption of the microbiome may potentiate inflammation and secondary brain injury (SBI). However, microbial-specific mediators and mechanisms remain unclear. METHODS Thirty-five consecutive patients with ABI admitted to the neuroscience critical care unit at the University of Chicago were prospectively studied. Injury severity at hospital admission was assessed using the Injury Severity Score (ISS) and the Glasgow Coma Scale (GCS). Final neurologic function was assessed via the Glasgow Outcome Score extended (GOSe). Serum, plasma, and stool targeted metabolomics, as well as stool shotgun metagenomics, were performed on longitudinal samples collected during hospitalization. RESULTS Multivariate analysis identified microbiome-modified metabolites that were positively and negatively associated with functional outcomes after ABI. Novel identification of conjugated bile acid (BA) species and vitamin B12 precursors indicative of outcome were detected in the first collected samples (within 48 hours). Network analysis revealed greater integration of negatively associated metabolites across tissues and identified tauro-α/μ-muricholic acid (TMCA) as central to the cross-tissue metabolomes. CONCLUSIONS Microbiome metabolites may be useful in assessing brain injury outcomes to inform treatment. Bile acid species transformed by the gut microbiome are predictive of ABI outcome.