Proteobacteria-Firmicutes correlations.

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）是一种患病率持续攀升的神经精神疾病，核心临床表现为多动、注意力涣散与冲动性。该疾病的症状源于神经环路的功能性缺陷，近年研究提示肠道微生物组（gut microbiome）在其发病机制中扮演了关键角色。肠道微生物组是一个由多种相互依存的微生物类群构成的复杂生态系统，其内部存在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密切关联，其中部分通路涉及与ADHD相关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对ADHD患者的肠道微生物组进行分析，并已提出若干在ADHD群体中丰度存在显著差异的微生物类群。然而，鲜有研究深入探究最终导致这些宏观指标出现差异的复杂底层动力学机制，致使当前相关研究图景仍存在大量空白，部分结论甚至相互矛盾，整体尚未形成统一定论。本研究旨在填补这一研究空白，我们不再局限于微生物类群的丰度分析，转而聚焦类群间的相互作用（即合作与竞争关系），采用一项公开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），检测手段为靶向16S rRNA基因v3-v4可变区的qPCR实验。我们首先开展了现有ADHD肠道微生物组研究中通用的宏观分析流程，包括多样性分析、差异丰度分析及菌群组成分析，以验证已有结论的一致性并挖掘潜在的新趋势。随后，我们基于SparCC相关性分析（p ≤ 0.01）分别构建了健康对照群体与ADHD患者群体的微生物共现网络（Microbial Co-occurrence Networks, MCNs），以此估算类群间的双向生态相互作用。我们通过群落检测算法识别出存在协同合作关系的微生物类群簇，并计算了各簇的质心；同时通过中心性分析估算出对整体肠道微生态至关重要的核心微生物类群。最后，我们对本研究的结果进行了系统性总结，就如何指导未来实验、优化本研究方法及该领域的通用研究启示提出了若干猜想与建议。