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从微生物中挖掘心理健康的宝藏:确定微生物代谢途径在人类大脑健康和疾病中的作用。

Mining microbes for mental health: Determining the role of microbial metabolic pathways in human brain health and disease.

机构信息

Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.

APC Microbiome Institute, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.

出版信息

Neurosci Biobehav Rev. 2021 Jun;125:698-761. doi: 10.1016/j.neubiorev.2021.02.044. Epub 2021 Mar 3.

Abstract

There is increasing knowledge regarding the role of the microbiome in modulating the brain and behaviour. Indeed, the actions of microbial metabolites are key for appropriate gut-brain communication in humans. Among these metabolites, short-chain fatty acids, tryptophan, and bile acid metabolites/pathways show strong preclinical evidence for involvement in various aspects of brain function and behaviour. With the identification of neuroactive gut-brain modules, new predictive tools can be applied to existing datasets. We identified 278 studies relating to the human microbiota-gut-brain axis which included sequencing data. This spanned across psychiatric and neurological disorders with a small number also focused on normal behavioural development. With a consistent bioinformatics pipeline, thirty-five of these datasets were reanalysed from publicly available raw sequencing files and the remainder summarised and collated. Among the reanalysed studies, we uncovered evidence of disease-related alterations in microbial metabolic pathways in Alzheimer's Disease, schizophrenia, anxiety and depression. Amongst studies that could not be reanalysed, many sequencing and technical limitations hindered the discovery of specific biomarkers of microbes or metabolites conserved across studies. Future studies are warranted to confirm our findings. We also propose guidelines for future human microbiome analysis to increase reproducibility and consistency within the field.

摘要

越来越多的研究表明,微生物组在调节大脑和行为方面发挥着重要作用。事实上,微生物代谢产物的作用对于人类肠道与大脑之间的适当通讯至关重要。在这些代谢产物中,短链脂肪酸、色氨酸和胆汁酸代谢物/途径在涉及大脑功能和行为的各个方面都具有很强的临床前证据。随着对肠道-大脑神经活性模块的识别,新的预测工具可以应用于现有数据集。我们确定了 278 项与人类微生物群-肠道-大脑轴相关的研究,其中包括测序数据。这些研究涵盖了精神和神经疾病,少数研究也集中在正常行为发育上。通过一致的生物信息学管道,我们从公开的原始测序文件中重新分析了其中的 35 个数据集,并对其余数据集进行了总结和整理。在重新分析的研究中,我们发现了阿尔茨海默病、精神分裂症、焦虑和抑郁等疾病相关的微生物代谢途径改变的证据。在无法重新分析的研究中,许多测序和技术限制阻碍了在整个研究中发现微生物或代谢物的特定生物标志物。需要进一步的研究来证实我们的发现。我们还提出了未来人类微生物组分析的指南,以提高该领域的可重复性和一致性。

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