Principal component error rates.

Attention Deficit Hyperactivity Disorder (ADHD) is an increasingly prevalent neuropsychiatric disorder characterized by hyperactivity, inattention, and impulsivity. Symptoms emerge from underlying deficiencies in neurocircuitry, and recent research has suggested a role played by the gut microbiome. The gut microbiome is an ecosystem of interdependent taxa involved in an exponentially complex web of interactions, plus host gene and reaction pathways, some of which involve neurotransmitters with roles in ADHD neurocircuitry. Studies have analyzed the ADHD gut microbiome using macroscale metrics such as diversity and differential abundance, and have proposed several taxa as elevated or reduced in ADHD compared to Control. Few studies have delved into the complex underlying dynamics ultimately responsible for the emergence of such metrics, leaving a largely incomplete, sometimes contradictory, and ultimately inconclusive picture. We aim to help complete this picture by venturing beyond taxa abundances and into taxa relationships (i.e. cooperation and competition), using a publicly available gut microbiome dataset (targeted 16S, v3-4 region, qPCR) from an observational, case-control study of 30 Control (15 female, 15 male) and 28 ADHD (15 female, 13 male) undergraduate students. We first perform the same macroscale analyses prevalent in ADHD gut microbiome literature (diversity, differential abundance, and composition) to observe the degree of correspondence, or any new trends. We then estimate two-way ecological relationships by producing Control and ADHD Microbial Co-occurrence Networks (MCNs), using SparCC correlations (p ≤ 0.01). We perform community detection to find clusters of taxa estimated to mutually cooperate along with their centroids, and centrality calculations to estimate taxa most vital to overall gut ecology. We finally summarize our results, providing conjectures on how they can guide future experiments, some methods for improving our experiments, and general implications for the field.

注意缺陷多动障碍（Attention Deficit Hyperactivity Disorder, ADHD）是一种日益流行的神经精神疾病，以多动、注意力涣散与冲动行为为核心特征。其症状源于神经环路的潜在功能缺陷，近期研究提示肠道菌群（gut microbiome）可能在疾病发生中发挥了关键作用。肠道菌群是由相互依存的微生物类群构成的生态系统，参与一张呈指数级复杂的相互作用网络，同时与宿主基因及代谢反应通路存在关联，其中部分通路涉及与ADHD神经环路功能相关的神经递质。已有研究通过多样性、差异丰度等宏观指标对ADHD患者的肠道菌群展开分析，并提出了若干在ADHD群体中丰度存在显著升高或降低的微生物类群。然而鲜有研究深入探究最终催生这类宏观指标的复杂底层动力学机制，这使得当前的研究图景大量缺失且时常相互矛盾，最终尚未形成定论。本研究旨在超越类群丰度分析范畴，转向微生物类群间相互关系（即协作与竞争）的研究，以完善这一研究图景。所用数据来自一项公开可得的肠道菌群数据集（靶向16S rRNA，v3-4区域，qPCR），该数据集源于一项针对30名健康对照者（15名女性、15名男性）与28名ADHD患者（15名女性、13名男性）本科生的观察性病例对照研究。本研究首先将开展ADHD肠道菌群相关文献中常见的宏观分析（多样性、差异丰度与群落组成分析），以观察现有研究结论的对应程度或发现新的研究趋势。随后，我们将利用SparCC相关性（p ≤ 0.01）构建健康对照者与ADHD患者的微生物共现网络（Microbial Co-occurrence Networks, MCNs），以此估算双向生态相互关系。我们将通过群落检测算法识别存在相互协作的微生物类群簇及其质心，并通过中心性计算来估算对整体肠道生态系统最为关键的微生物类群。最后，我们将总结本次研究的结果，就该结果如何指导未来实验、改进本研究的若干方法，以及该研究领域的总体启示提出相应推测。