Mixed-family clusters.

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.注意缺陷与多动障碍（Attention Deficit Hyperactivity Disorder, ADHD）是一种愈发高发的神经精神疾病，以多动、注意力缺陷及冲动行为为核心临床特征，其症状源于神经环路的潜在功能缺陷，近年研究提示肠道微生物组（gut microbiome）在该病的发生发展中发挥着关键调控作用。肠道微生物组是由相互依存的微生物类群构成的复杂生态系统，参与构建一张指数级复杂的相互作用网络，同时与宿主基因及代谢通路紧密关联，其中部分通路涉及与ADHD神经环路功能相关的神经递质。现有研究多采用多样性、差异丰度等宏观指标分析ADHD患者的肠道微生物组，并提出了若干在ADHD患者中丰度较健康对照升高或降低的微生物类群，但鲜有研究深入探究最终催生上述宏观指标的复杂底层动态机制，导致当前学界对该领域的认知尚不完整，甚至时常存在矛盾，最终尚未形成定论。本研究旨在弥补这一认知缺口：我们跳出仅关注类群丰度的传统研究范式，转而聚焦类群间的相互作用（即协作与竞争关系），使用一项公开可得的肠道微生物组数据集，该数据集来自一项针对本科生群体的观察性病例对照研究，共纳入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），检测方法为靶向16S rRNA基因v3-v4区域的定量聚合酶链反应（quantitative Polymerase Chain Reaction, qPCR）。我们首先开展ADHD肠道微生物组相关文献中常见的宏观分析（包括多样性分析、差异丰度分析及群落组成分析），以观察本次研究结果与既有文献的契合程度，或发现新的研究趋势；随后，我们借助SparCC相关分析（p ≤ 0.01）构建健康对照与ADHD患者的微生物共现网络（Microbial Co-occurrence Networks, MCNs），以此准确估算类群间的双向生态相互作用；我们进一步执行群落检测，以识别存在相互协作的微生物类群簇及其质心，并通过中心性分析估算对整体肠道生态系统最为关键的核心类群；最后，我们对研究结果进行系统总结，提出可指导未来实验的科学推测、若干优化本研究方法的可行路径，以及该领域的一般性研究启示。