肠道微生物群作为改善创伤性脑损伤的生化、神经解剖学和行为影响的治疗靶点。
Gut Microbiota as a Therapeutic Target to Ameliorate the Biochemical, Neuroanatomical, and Behavioral Effects of Traumatic Brain Injuries.
作者信息
Rice Matthew W, Pandya Jignesh D, Shear Deborah A
机构信息
Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
出版信息
Front Neurol. 2019 Aug 16;10:875. doi: 10.3389/fneur.2019.00875. eCollection 2019.
Current efficacious treatments for traumatic brain injury (TBI) are lacking. Establishment of a protective gut microbiota population offers a compelling therapeutic avenue, as brain injury induces disruptions in the composition of the gut microbiota, i.e., gut dysbiosis, which has been shown to contribute to TBI-related neuropathology and impaired behavioral outcomes. The gut microbiome is involved in the modulation of a multitude of cellular and molecular processes fundamental to the progression of TBI-induced pathologies including neuroinflammation, blood brain barrier permeability, immune system response, microglial activation, and mitochondrial dysfunction, as well as intestinal motility and permeability. Additionally, gut dysbiosis further aggravates behavioral impairments in animal models of TBI and spinal cord injury, as well as negatively affects health outcomes in murine stroke models. Recent studies indicate that microbiota transplants and probiotics ameliorate neuroanatomical damage and functional impairments in animal models of stroke and spinal cord injury. In addition, probiotics have been shown to reduce the rate of infection and time spent in intensive care of hospitalized patients suffering from brain trauma. Perturbations in the composition of the gut microbiota and its metabolite profile may also serve as potential diagnostic and theragnostic biomarkers for injury severity and progression. This review aims to address the etiological role of the gut microbiome in the biochemical, neuroanatomical, and behavioral/cognitive consequences of TBI, as well as explore the potential of gut microbiome manipulation in the form of probiotics as an effective therapeutic to ameliorate TBI-induced pathology and symptoms.
目前缺乏针对创伤性脑损伤(TBI)的有效治疗方法。建立具有保护作用的肠道微生物群提供了一条引人注目的治疗途径,因为脑损伤会导致肠道微生物群组成的破坏,即肠道菌群失调,这已被证明会导致与TBI相关的神经病理学和行为结果受损。肠道微生物群参与调节多种细胞和分子过程,这些过程对于TBI诱导的病理进展至关重要,包括神经炎症、血脑屏障通透性、免疫系统反应、小胶质细胞激活和线粒体功能障碍,以及肠道运动和通透性。此外,肠道菌群失调会进一步加重TBI和脊髓损伤动物模型中的行为障碍,并对小鼠中风模型的健康结果产生负面影响。最近的研究表明,微生物群移植和益生菌可改善中风和脊髓损伤动物模型中的神经解剖损伤和功能障碍。此外,益生菌已被证明可以降低脑外伤住院患者的感染率和重症监护时间。肠道微生物群组成及其代谢物谱的扰动也可能作为损伤严重程度和进展的潜在诊断和治疗生物标志物。本综述旨在探讨肠道微生物群在TBI的生化、神经解剖和行为/认知后果中的病因作用,并探索以益生菌形式操纵肠道微生物群作为改善TBI诱导的病理和症状的有效治疗方法的潜力。