Upper-level ATria rankings.

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）是一种愈发高发的神经精神疾病，以多动、注意力不集中及冲动行为为核心特征。该病的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在其发生发展中发挥了一定作用。肠道菌群是由相互依存的微生物分类群构成的生态系统，其相互作用网络呈指数级复杂，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神经环路功能相关的神经递质。既往研究多采用多样性、差异丰度等宏观指标对ADHD患者的肠道菌群进行分析，并提出相较于健康对照组，ADHD患者体内存在若干丰度异常升高或降低的微生物分类群。但鲜有研究深入探究驱动上述宏观指标变化的复杂底层生态动力学机制，导致当前相关研究图景整体尚不完整，甚至存在部分矛盾之处，最终难以得出确定性结论。本研究旨在突破仅关注微生物分类群丰度的研究框架，转而聚焦分类群间的相互作用（即协同与竞争关系），以期完善当前的研究图景。我们使用了一项公开的肠道菌群数据集，该数据来自一项针对30名健康对照（15名女性、15名男性）及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，其检测方法为靶向16S rRNA基因v3-v4可变区的测序结合实时荧光定量PCR（qPCR）。我们首先开展了ADHD肠道菌群相关文献中常见的宏观分析，包括多样性分析、差异丰度分析及菌群组成分析，以验证现有研究结论的一致性，并挖掘潜在的新趋势。随后我们采用SparCC相关分析（p ≤ 0.01）构建健康对照组与ADHD患者的微生物共现网络（Microbial Co-occurrence Networks, MCNs），以此估算分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互作的分类群聚类及其质心，并通过中心性分析估算出对整体肠道菌群生态至关重要的核心分类群。最后我们对研究结果进行总结，就该结果如何指导后续实验、优化本研究方法，以及该领域的通用研究启示提出了若干推测性观点。