Antibiotic treatment following controlled brain injuries in male mice produced smaller lesion volumes, reduced cell death, and decreased neuroinflammation compared to untreated controls. The protective effects were most pronounced after repeated injuries, despite antibiotics dramatically altering gut microbial diversity and reducing short-chain fatty acid production. Two bacterial species, Parasutterella excrementihominis and Lactobacillus johnsonii, persisted through antibiotic treatment, potentially mediating the neuroprotective benefits.
This counterintuitive finding challenges the prevailing wisdom that gut microbiome disruption worsens neurological outcomes. The gut-brain axis research has consistently shown that beneficial bacteria and their metabolites like SCFAs support brain health, yet here we see brain protection despite SCFA depletion. This suggests alternative microbial pathways may drive post-injury neuroinflammation—perhaps through bacterial toxins or immune-activating compounds that antibiotics eliminate. The contrast with germ-free mice showing worse outcomes indicates the surviving microbial remnants, rather than complete sterilization, provide optimal neuroprotection. While promising for acute brain injury treatment, this approach requires careful consideration given antibiotics' well-documented risks to long-term microbiome health and antibiotic resistance.