Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, China.
Front Immunol. 2022 Jul 13;13:781148. doi: 10.3389/fimmu.2022.781148. eCollection 2022.
The intestinal microbiota regulate the brain function of the host through the production of a myriad of metabolites and are associated with various neurological diseases. Understanding the intestinal microbiome of patients with prolonged disorders of consciousness (DoC) is important for the evaluation and treatment of the disease. To investigate the differences in the intestinal microbiome and short-chain fatty acids (SCFAs) among patients in a vegetative state (VS), a minimally conscious state (MCS), and emerged from MCS (EMCS), as well as the influence of antibiotics on these patients, 16S ribosomal RNA (16S rRNA) sequencing and targeted lipidomics were performed on fecal samples from patients; in addition, analysis of the electroencephalogram (EEG) signals was performed to evaluate the brain function of these patients. The results showed that the intestinal microbiome of the three groups differed greatly, and some microbial communities showed a reduced production of SCFAs in VS patients compared to the other two groups. Moreover, reduced microbial communities and five major SCFAs, along with attenuated brain functional connectivity, were observed in MCS patients who were treated with antibiotics compared to those who did not receive antibiotic treatment, but not in the other pairwise comparisons. Finally, three genus-level microbiota-, and -were considered as potential biomarkers to distinguish MCS from VS patients, with high accuracy both in the discovery and validation cohorts. Together, our findings improved the understanding of patients with prolonged DoC from the intestinal microbiome perspective and provided a new reference for the exploration of therapeutic targets.
肠道微生物群通过产生大量代谢物来调节宿主的大脑功能，并且与各种神经疾病有关。了解持续性意识障碍（DOC）患者的肠道微生物群对于评估和治疗该疾病非常重要。为了研究植物状态（VS）、最小意识状态（MCS）和从 MCS 中苏醒的患者（EMCS）之间的肠道微生物群和短链脂肪酸（SCFA）的差异，以及抗生素对这些患者的影响，对患者粪便样本进行了 16S 核糖体 RNA（16S rRNA）测序和靶向脂质组学分析；此外，还对脑电图（EEG）信号进行了分析，以评估这些患者的大脑功能。结果表明，三组患者的肠道微生物群差异很大，与其他两组相比，一些微生物群落中 SCFA 的产生减少。此外，与未接受抗生素治疗的患者相比，接受抗生素治疗的 MCS 患者的微生物群落减少，并且五种主要的 SCFAs 减少，大脑功能连接减弱，但在其他两两比较中则没有观察到这种情况。最后，三个属水平的微生物群和被认为是区分 MCS 和 VS 患者的潜在生物标志物，在发现和验证队列中都具有较高的准确性。总之，我们的研究结果从肠道微生物群的角度提高了对持续性意识障碍患者的理解，并为探索治疗靶点提供了新的参考。
