Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
PLoS One. 2022 Nov 30;17(11):e0278259. doi: 10.1371/journal.pone.0278259. eCollection 2022.
Dysregulation of the gut microbiome has been shown to perpetuate neuroinflammation, alter intestinal permeability, and modify repetitive mild traumatic brain injury (RmTBI)-induced deficits. However, there have been no investigations regarding the comparative effects that the microbiome may have on RmTBI in adolescents and adults. Therefore, we examined the influence of microbiome depletion prior to RmTBI on microbial composition and metabolome, in adolescent and adult Sprague Dawley rats. Rats were randomly assigned to standard or antibiotic drinking water for 14 days, and to subsequent sham or RmTBIs. The gut microbiome composition and metabolome were analysed at baseline, 1 day after the first mTBI, and at euthanasia (11 days following the third mTBI). At euthanasia, intestinal samples were also collected to quantify tight junction protein (TJP1 and occludin) expression. Adolescents were significantly more susceptible to microbiome depletion via antibiotic administration which increased pro-inflammatory composition and metabolites. Furthermore, RmTBI induced a transient increase in 'beneficial bacteria' (Lachnospiraceae and Faecalibaculum) in only adolescents that may indicate compensatory action in response to the injury. Finally, microbiome depletion prior to RmTBI generated a microbiome composition and metabolome that exemplified a potentially chronic pathogenic and inflammatory state as demonstrated by increased Clostridium innocuum and Erysipelatoclostridium and reductions in Bacteroides and Clostridium Sensu Stricto. Results highlight that adolescents are more vulnerable to RmTBI compared to adults and dysbiosis prior to injury may exacerbate secondary inflammatory cascades.
肠道微生物组的失调已被证明会持续引发神经炎症，改变肠道通透性，并改变重复性轻度创伤性脑损伤（RmTBI）引起的损伤。然而，尚未有研究探讨微生物组对青少年和成年人 RmTBI 的比较影响。因此，我们研究了 RmTBI 前微生物组耗竭对青少年和成年 Sprague Dawley 大鼠微生物组成和代谢组的影响。大鼠被随机分配到标准或抗生素饮用水中 14 天，并随后进行假手术或 RmTBI。在基线、第一次 mTBI 后 1 天和安乐死时（第三次 mTBI 后 11 天）分析肠道微生物组组成和代谢组。安乐死时，还收集肠组织样本以定量紧密连接蛋白（TJP1 和 occludin）的表达。青少年通过抗生素给药更容易受到微生物组耗竭的影响，这增加了促炎成分和代谢物。此外，RmTBI 仅在青少年中诱导“有益细菌”（Lachnospiraceae 和 Faecalibaculum）的短暂增加，这可能表明是对损伤的代偿反应。最后，RmTBI 前的微生物组耗竭产生了一种微生物组组成和代谢组，其表现出潜在的慢性致病和炎症状态，这表现为梭菌属和肠球菌属的增加以及拟杆菌属和梭菌属的减少。结果表明，与成年人相比，青少年对 RmTBI 更敏感，损伤前的失调可能会加剧继发性炎症级联反应。
