Traumatic brain injury induces neuroinflammation and gut microbiome dysbiosis, yet the effects of short-term antibiotic treatment on these processes remain poorly understood. To address this, male mice received controlled brain injuries followed by a brief course of oral antibiotics. Antibiotic treatment reduced bacterial abundance in feces and altered microbial diversity, with more pronounced shifts after two injuries. Despite this disruption, antibiotic-treated mice exhibited smaller lesion volumes, reduced cell death, attenuated microglial and macrophage activation, lower pro-inflammatory cytokine levels, and decreased astrogliosis and peripheral immune cell infiltration compared with vehicle-treated mice after two injuries. In the gut, increasing injury severity was associated with villus shortening and loss of mucus-producing cells, and antibiotic treatment further modified these injury-related changes. Circulating levels of short-chain fatty acids and associated microbial metabolic functions were reduced by antibiotic exposure. In contrast, germ-free mice showed increased lesion volumes and exacerbated gliosis following brain injury. Long-read metagenomic sequencing identified Parasutterella excrementihominis and Lactobacillus johnsonii as taxa that persisted despite antibiotic treatment. Collectively, these results suggest that antibiotics can reduce brain damage after injury through mechanisms not explained by short-chain fatty acids, while also highlighting potential drawbacks of altering the gut microbiome. Short-term oral antibiotics reshape the gut microbiome after single or repeated TBI in male mice, yet reduce lesion volume, apoptosis, gliosis, cytokines, and immune infiltration, revealing SCFA-independent neuroprotection with translational trade-offs.
Flinn et al. (Wed,) studied this question.