Obrenovich Mark, Jaworski Hayden, Tadimalla Tara, Mistry Adil, Sykes Lorraine, Perry George, Bonomo Robert A
Research Service, Louis Stokes Cleveland, Department of Veteran's Affairs Medical Center, Cleveland, OH 44106, USA.
Departments of Chemistry, Biochemistry, Pathology and Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
Microorganisms. 2020 May 23;8(5):784. doi: 10.3390/microorganisms8050784.
The human gut hosts a wide and diverse ecosystem of microorganisms termed the microbiota, which line the walls of the digestive tract and colon where they co-metabolize digestible and indigestible food to contribute a plethora of biochemical compounds with diverse biological functions. The influence gut microbes have on neurological processes is largely yet unexplored. However, recent data regarding the so-called leaky gut, leaky brain syndrome suggests a potential link between the gut microbiota, inflammation and host co-metabolism that may affect neuropathology both locally and distally from sites where microorganisms are found. The focus of this manuscript is to draw connection between the microbiota-gut-brain (MGB) axis, antibiotics and the use of "BUGS AS DRUGS" for neurodegenerative diseases, their treatment, diagnoses and management and to compare the effect of current and past pharmaceuticals and antibiotics for alternative mechanisms of action for brain and neuronal disorders, such as Alzheimer disease (AD), Amyotrophic Lateral Sclerosis (ALS), mood disorders, schizophrenia, autism spectrum disorders and others. It is a paradigm shift to suggest these diseases can be largely affected by unknown aspects of the microbiota. Therefore, a future exists for applying microbial, chemobiotic and chemotherapeutic approaches to enhance translational and personalized medical outcomes. Microbial modifying applications, such as CRISPR technology and recombinant DNA technology, among others, echo a theme in shifting paradigms, which involve the gut microbiota (GM) and mycobiota and will lead to potential gut-driven treatments for refractory neurologic diseases.
人类肠道中存在着一个广泛多样的微生物生态系统,称为微生物群,它们排列在消化道和结肠壁上,在那里它们共同代谢可消化和不可消化的食物,产生大量具有多种生物学功能的生化化合物。肠道微生物对神经过程的影响在很大程度上尚未得到探索。然而,最近有关所谓的肠漏、脑漏综合征的数据表明,肠道微生物群、炎症和宿主共同代谢之间可能存在联系,这可能会在局部和远离微生物所在部位的远端影响神经病理学。本手稿的重点是建立微生物群-肠道-大脑(MGB)轴、抗生素与将“细菌作为药物”用于神经退行性疾病及其治疗、诊断和管理之间的联系,并比较当前和过去的药物及抗生素对大脑和神经元疾病(如阿尔茨海默病(AD)、肌萎缩侧索硬化症(ALS)、情绪障碍、精神分裂症、自闭症谱系障碍等)的替代作用机制的影响。认为这些疾病可能在很大程度上受到微生物群未知方面的影响,这是一种范式转变。因此,应用微生物、化学益生菌和化学治疗方法来提高转化医学和个性化医疗效果的前景是存在的。微生物修饰应用,如CRISPR技术和重组DNA技术等,呼应了一种范式转变的主题,其中涉及肠道微生物群(GM)和真菌微生物群,并将为难治性神经系统疾病带来潜在的肠道驱动治疗方法。