Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy.

IF 5.7 2区 生物学
Rebecca F Slykerman, Naomi Davies, Klara Vlckova, Kenneth J O'Riordan, Shalome A Bassett, James Dekker, Harriët Schellekens, Niall P Hyland, Gerard Clarke, Elaine Patterson
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引用次数: 0

Abstract

Advancing microbiome-gut-brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of the gut microbiome as a tractable therapeutic target for gastrointestinal, mental and brain health. Current research is still marked by many open questions that undermine widespread application to humans. For example, the lack of mechanistic understanding of probiotic effects means it remains unclear why even apparently closely related strains exhibit different effects in vivo. For the therapeutic application of live microbial psychobiotics, consensus on their application as adjunct treatments to conventional neuromodulators, use in unmedicated populations or in at-risk cohorts with sub-clinical symptomatology is warranted. This missing information on both sides of the therapeutic equation when treating central nervous system (CNS) conditions makes psychobiotic research challenging, especially when compared to other pharmaceutical or functional food approaches. Expediting the transition from positive preclinical data to proven benefits in humans includes interpreting the promises and pitfalls of animal behavioural assays, as well as navigating mechanism-informed decision making to select the right microbe(s) for the job. In this review, we consider how these decisions can be supported in light of information accrued from a range of clinical studies across healthy, at-risk and pathological study populations, where specific strains have been evaluated in the context of gastrointestinal physiology, brain function and behaviour. Examples of successful, partial and unsuccessful translation from bench to bedside are considered. We also discuss the developments in in silico analyses that have enhanced our understanding of the gut microbiome and that have moved research towards pinpointing the host-microbe interactions most important for optimal gut-brain axis function. Combining this information with knowledge from functional assays across in vitro and ex vivo domains and incorporating model organisms can prime the discovery pipelines with the most promising and rationally selected psychobiotic candidates.

用于肠-脑轴健康的精确精神制剂:推进发现管道,以提供机制途径和已证实的健康功效。
推进微生物组-肠-脑轴科学需要系统、合理和转化的方法来弥合目前阻碍肠道微生物组作为胃肠道、精神和大脑健康的可处理治疗靶点的充分利用的关键知识差距。目前的研究仍然存在许多悬而未决的问题,这些问题阻碍了对人类的广泛应用。例如,缺乏对益生菌作用的机制理解意味着为什么即使是明显密切相关的菌株在体内也表现出不同的作用仍然不清楚。对于活微生物精神生物制剂的治疗应用,有必要就其作为常规神经调节剂的辅助治疗、用于未用药人群或亚临床症状的高危人群达成共识。在治疗中枢神经系统(CNS)疾病时,治疗方程两边的信息缺失使得精神生物学研究具有挑战性,特别是与其他药物或功能食品方法相比。加速从积极的临床前数据到人类已证实的益处的转变,包括解释动物行为分析的前景和缺陷,以及引导机制知情的决策,以选择合适的微生物。在这篇综述中,我们考虑如何根据从健康、危险和病理研究人群的一系列临床研究中积累的信息来支持这些决定,在这些研究中,特定菌株已经在胃肠道生理学、脑功能和行为的背景下进行了评估。本文考虑了成功的、部分的和不成功的从实验室到床边的翻译的例子。我们还讨论了计算机分析的发展,这些分析增强了我们对肠道微生物组的理解,并将研究推向了确定宿主-微生物相互作用对最佳肠-脑轴功能最重要的方向。将这些信息与来自体外和离体领域的功能分析的知识结合起来,并结合模式生物,可以为最有希望和合理选择的精神生物学候选药物的发现管道提供基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Microbial Biotechnology
Microbial Biotechnology Immunology and Microbiology-Applied Microbiology and Biotechnology
CiteScore
11.20
自引率
3.50%
发文量
162
审稿时长
1 months
期刊介绍: Microbial Biotechnology publishes papers of original research reporting significant advances in any aspect of microbial applications, including, but not limited to biotechnologies related to: Green chemistry; Primary metabolites; Food, beverages and supplements; Secondary metabolites and natural products; Pharmaceuticals; Diagnostics; Agriculture; Bioenergy; Biomining, including oil recovery and processing; Bioremediation; Biopolymers, biomaterials; Bionanotechnology; Biosurfactants and bioemulsifiers; Compatible solutes and bioprotectants; Biosensors, monitoring systems, quantitative microbial risk assessment; Technology development; Protein engineering; Functional genomics; Metabolic engineering; Metabolic design; Systems analysis, modelling; Process engineering; Biologically-based analytical methods; Microbially-based strategies in public health; Microbially-based strategies to influence global processes
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