Decoding Microbiome Research for Clinical Psychiatry

J. Foster
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引用次数: 3

Abstract

It is remarkable to see how fast and furious microbiome research over the past decade has advanced to the forefront of neuroscience and psychiatry. From an insider’s perspective, there are several reasons to consider the microbiome in clinical psychiatry: (1) to identify biomarkers related to biological differences that allow us to identify subgroups of clinical populations and improve the ability to match individuals to the best treatment, (2) to identify individuals at risk for early intervention, (3) to provide novel targets for drug development, and (4) to facilitate the expansion and new development of microbiome-targeted therapies including, but not limited to, diet, prebiotics, and probiotics. An individual’s microbiome is their own, and the colonization of all surfaces of our body that begins at birth continues through early life. The diversity, composition, and function of an individual’s microbiome are influenced early in life by mode of delivery, breast milk versus formula, exposure to antibiotics and nonantibiotic drugs, sex, diet, stress, housing conditions, and geography. Our own genetics influences our microbiome, and gene–environment interactions over life influence the microbe–host interactions that impact host physiological processes. Advances in our understanding of the microbiome in health and disease are promising. Media, public, academics, and health-care providers are challenged to understand this dynamic area of research and to implement best practices to improve treatment approaches in mental health. In a recent issue of The Canadian Journal of Psychiatry, Butler et al. provide an excellent overview of recent microbiome research and advice on best practices in clinical psychiatry related to the microbiome. For neuroscience and psychiatry, a few key studies using germ-free mice provided the spark for neuroscientists to consider how microbes may influence brain function. As additional neuroscientists considered the microbiome, new results demonstrated that the microbe–host interactions and signaling of the microbiota–gut–brain axis influence neurodevelopment, neuroplasticity, neurotransmitter systems, neurogenesis, many behavioral phenotypes, and more. Based on this preclinical work, interest in understanding a role for the microbiome in clinical psychiatry has recently emerged. As reviewed in the study of Butler et al., alterations in microbiota composition have been reported in major depressive disorder, bipolar affective disorder, anxiety disorders, schizophrenia and psychotic disorders, neurodegenerative disorders, and autism spectrum disorder. While differences between diagnostic groups and healthy volunteers have been observed, identifying key taxa and the functional microbial pathways that influence host physiology is an essential step to advance the translation of microbiome research to clinical applications. To date, many studies have relied on 16S rRNA gene sequencing and analytical tools that limit the specificity of taxa identified resulting in poor reproducibility of health-related bacterial taxa across studies. 16S rRNA sequencing only identifies taxa to the genus level and provides no direct insight into the functional changes of microbiota that may be driving effects on host physiology. Additional approaches include shotgun metagenomics and metabolomics. Shotgun metagenomics sequencing provides not only who is there but gives functional readouts of bacterial metabolism. Metabolomics examines the metabolites of the bacteria and/or the host. As noted in the study of Butler et al., short chain fatty acids (SCFAs) are important bacterial metabolites produced by gut bacteria that influence other commensals and are important to gut physiology as well as part of microbiota–host signaling systems that extend beyond the gut. Beyond SCFAs, microbially derived molecules include neurotransmitters, indoles, bile acids, choline metabolites, lactate, and vitamins, and evidence is accumulating that the microbial metabolites may
解码微生物组研究临床精神病学
在过去的十年里,微生物组的研究是如何迅速而激烈地发展到神经科学和精神病学的前沿,这是值得注意的。从内部人士的角度来看,在临床精神病学中考虑微生物组有几个原因:(1)识别与生物学差异相关的生物标志物,使我们能够识别临床人群的亚群,并提高个体与最佳治疗相匹配的能力;(2)识别有早期干预风险的个体;(3)为药物开发提供新的靶点;(4)促进微生物组靶向治疗的扩展和新开发,包括但不限于饮食、益生元和益生菌。每个人的微生物群都是他们自己的,从出生开始,我们身体所有表面的定植一直持续到生命早期。个体微生物组的多样性、组成和功能在生命早期受到分娩方式、母乳还是配方奶、抗生素和非抗生素药物暴露、性别、饮食、压力、住房条件和地理位置的影响。我们自身的遗传影响着我们的微生物群,而生命中基因与环境的相互作用影响着微生物与宿主的相互作用,而这些相互作用又影响着宿主的生理过程。我们对微生物群在健康和疾病方面的理解有了很大的进展。媒体、公众、学术界和卫生保健提供者面临的挑战是了解这一动态研究领域,并实施最佳做法,以改进精神卫生治疗方法。在最近一期的《加拿大精神病学杂志》中,Butler等人对最近的微生物组研究进行了极好的概述,并就与微生物组相关的临床精神病学最佳实践提出了建议。对于神经科学和精神病学,一些使用无菌小鼠的关键研究为神经科学家提供了思考微生物如何影响大脑功能的火花。随着更多的神经科学家考虑微生物组,新的结果表明,微生物-宿主相互作用和微生物-肠-脑轴的信号传导影响神经发育、神经可塑性、神经递质系统、神经发生、许多行为表型等。基于这项临床前工作,最近出现了对理解微生物组在临床精神病学中的作用的兴趣。正如Butler等人的研究所述,在重度抑郁症、双相情感障碍、焦虑症、精神分裂症和精神病、神经退行性疾病和自闭症谱系障碍中已经报道了微生物群组成的改变。虽然已经观察到诊断组和健康志愿者之间的差异,但确定影响宿主生理的关键分类群和功能微生物途径是推进微生物组研究向临床应用转化的重要一步。迄今为止,许多研究依赖于16S rRNA基因测序和分析工具,这限制了所鉴定分类群的特异性,导致研究中与健康相关的细菌分类群的可重复性较差。16S rRNA测序只能识别属水平的分类群,并不能直接了解微生物群的功能变化,这些变化可能会对宿主生理产生影响。其他方法包括霰弹枪宏基因组学和代谢组学。霰弹枪宏基因组测序不仅提供了谁在那里,还提供了细菌代谢的功能读数。代谢组学检查细菌和/或宿主的代谢物。正如Butler等人的研究所指出的,短链脂肪酸(SCFAs)是肠道细菌产生的重要细菌代谢物,影响其他共生体,对肠道生理以及延伸到肠道之外的微生物-宿主信号系统的一部分很重要。除了短链脂肪酸,微生物衍生的分子包括神经递质、吲哚、胆汁酸、胆碱代谢物、乳酸和维生素,越来越多的证据表明微生物代谢物可能
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