Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Neurotrauma. 2021 Sep 15;38(18):2610-2621. doi: 10.1089/neu.2020.7506. Epub 2021 Jun 7.
Traumatic brain injury (TBI) alters microbial populations present in the gut, which may impact healing and tissue recovery. However, the duration and impact of these changes on outcome from TBI are unknown. Short-chain fatty acids (SCFAs), produced by bacterial fermentation of dietary fiber, are important signaling molecules in the microbiota gut-brain axis. We hypothesized that TBI would lead to a sustained reduction in SCFA producing bacteria, fecal SCFAs concentration, and administration of soluble SCFAs would improve functional outcome after TBI. Adult mice ( = 10) had the controlled cortical impact (CCI) model of TBI performed (6 m/sec, 2-mm depth, 50-msec dwell). Stool samples were collected serially until 28 days after CCI and analyzed for SCFA concentration by high-performance liquid chromatography-mass spectrometry/mass spectrometry and microbiome analyzed by 16S gene sequencing. In a separate experiment, mice ( = 10/group) were randomized 2 weeks before CCI to standard drinking water or water supplemented with the SCFAs acetate (67.5 mM), propionate (25.9 mM), and butyrate (40 mM). Morris water maze performance was assessed on post-injury Days 14-19. Alpha diversity remained stable until 72 h, at which point a decline in diversity was observed without recovery out to 28 days. The taxonomic composition of post-TBI fecal samples demonstrated depletion of bacteria from , , and families, and enrichment of bacteria from the family. Analysis from paired fecal samples revealed a reduction in total SCFAs at 24 h and 28 days after TBI. Acetate, the most abundant SCFA detected in the fecal samples, was reduced at 7 days and 28 days after TBI. SCFA administration improved spatial learning after TBI versus standard drinking water. In conclusion, TBI is associated with reduced richness and diversity of commensal microbiota in the gut and a reduction in SCFAs detected in stool. Supplementation of soluble SCFAs improves spatial learning after TBI.
创伤性脑损伤 (TBI) 改变了肠道中存在的微生物种群，这可能会影响愈合和组织恢复。然而，这些变化对 TBI 结果的持续时间和影响尚不清楚。短链脂肪酸 (SCFA) 是膳食纤维细菌发酵的重要信号分子，是微生物群-肠-脑轴中的重要信号分子。我们假设 TBI 会导致 SCFA 产生菌、粪便 SCFA 浓度持续减少，而给予可溶性 SCFA 会改善 TBI 后的功能结果。成年小鼠 ( = 10) 接受了控制性皮质撞击 (CCI) 模型的 TBI 处理 (6 m/sec，2-mm 深度，50-msec 停留)。在 CCI 后 28 天内连续采集粪便样本，并通过高效液相色谱-质谱/质谱分析 SCFA 浓度和 16S 基因测序分析微生物组。在另一个实验中，小鼠 ( = 10/组) 在 CCI 前 2 周随机分为标准饮用水或补充 SCFA 乙酸盐 (67.5 mM)、丙酸盐 (25.9 mM) 和丁酸盐 (40 mM) 的水。在损伤后第 14-19 天进行 Morris 水迷宫测试。直到 72 h，α多样性仍保持稳定，此后观察到多样性下降，直到 28 天没有恢复。TBI 后粪便样本的分类组成显示 、 和 科的细菌减少， 科的细菌富集。来自配对粪便样本的分析显示，TBI 后 24 h 和 28 天总 SCFA 减少。粪便样本中检测到的最丰富的 SCFA 乙酸盐在 TBI 后 7 天和 28 天减少。与标准饮用水相比，SCFA 给药改善了 TBI 后的空间学习。总之，TBI 与肠道共生微生物群落丰富度和多样性降低以及粪便中 SCFA 减少有关。补充可溶性 SCFA 可改善 TBI 后的空间学习。
