Flinn Hannah, Marshall Austin, Holcomb Morgan, Cruz Leonardo, Soriano Sirena, Treangen Todd J, Villapol Sonia
Houston Methodist Research Institute.
Rice University.
Res Sq. 2024 Jun 11:rs.3.rs-4475195. doi: 10.21203/rs.3.rs-4475195/v1.
The gut microbiome is linked to brain pathology in cases of traumatic brain injury (TBI), yet the specific bacteria that are implicated are not well characterized. To address this gap, in this study, we induced traumatic brain injury (TBI) in male C57BL/6J mice using the controlled cortical impact (CCI) injury model. After 35 days, we administered a broad-spectrum antibiotics (ABX) cocktail (ampicillin, gentamicin, metronidazole, vancomycin) through oral gavage for 2 days to diminish existing microbiota. Subsequently, we inflicted a second TBI on the mice and analyzed the neuropathological outcomes five days later.
Longitudinal analysis of the microbiome showed significant shifts in the diversity and abundance of bacterial genera during both acute and chronic inflammation. These changes were particularly dramatic following treatment with ABX and after the second TBI. ABX treatment did not affect the production of short-chain fatty acids (SCFA) but did alter intestinal morphology, characterized by reduced villus width and a lower count of goblet cells, suggesting potential negative impacts on intestinal integrity. Nevertheless, diminishing the intestinal microbiome reduced cortical damage, apoptotic cell density, and microglial/macrophage activation in the cortical and thalamic regions of the brain.
Our findings suggest that eliminating colonized gut bacteria via broad-spectrum ABX reduces neuroinflammation and enhances neurological outcomes in TBI despite implications to gut health.
在创伤性脑损伤（TBI）病例中，肠道微生物群与脑病理学相关，但其中涉及的特定细菌尚未得到充分表征。为了填补这一空白，在本研究中，我们使用控制性皮质撞击（CCI）损伤模型在雄性C57BL/6J小鼠中诱导创伤性脑损伤（TBI）。35天后，我们通过口服灌胃给予广谱抗生素（ABX）鸡尾酒（氨苄青霉素、庆大霉素、甲硝唑、万古霉素）2天，以减少现有的微生物群。随后，我们再次对小鼠造成TBI，并在五天后分析神经病理学结果。
对微生物群的纵向分析表明，在急性和慢性炎症期间，细菌属的多样性和丰度发生了显著变化。在用ABX治疗后以及第二次TBI后，这些变化尤为显著。ABX治疗不影响短链脂肪酸（SCFA）的产生，但确实改变了肠道形态，其特征是绒毛宽度减小和杯状细胞数量减少，这表明对肠道完整性可能有负面影响。然而，减少肠道微生物群可减少大脑皮质和丘脑区域的皮质损伤、凋亡细胞密度以及小胶质细胞/巨噬细胞激活。
我们的研究结果表明，尽管对肠道健康有影响，但通过广谱ABX消除定植的肠道细菌可减轻TBI中的神经炎症并改善神经学结果。
