Jakobi Babette, Vlaming Priscilla, Mulder Danique, Ribases Marta, Richarte Vanesa, Ramos-Quiroga Josep Antoni, Tendolkar Indira, van Eijndhoven Philip, Vrijsen Janna N, Buitelaar Jan, Franke Barbara, Hoogman Martine, Bloemendaal Mirjam, Arias-Vasquez Alejandro
medRxiv. 2023 Dec 18:2023.12.18.23300126. doi: 10.1101/2023.12.18.23300126.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that persists into adulthood in the majority of individuals. While the gut-microbiome seems to be relevant for ADHD, the few publications on gut-microbial alterations in ADHD are inconsistent, in the investigated phenotypes, sequencing method/region, preprocessing, statistical approaches, and findings. To identify gut-microbiome alterations in adult ADHD, robust across studies and statistical approaches, we harmonized bioinformatic pipelines and analyses of raw 16S rRNA sequencing data from four adult ADHD case-control studies (N =312, N =305). We investigated diversity and differential abundance of selected genera (logistic regression and ANOVA-like Differential Expression tool), corrected for age and sex, and meta-analyzed the study results. Converging results were investigated for association with hyperactive/impulsive and inattentive symptoms across all participants. Beta diversity was associated with ADHD diagnosis but showed significant heterogeneity between cohorts, despite harmonized analyses. Several genera were robustly associated with adult ADHD; e.g., (LogOdds=0.17, p =4.42×10 ), which was more abundant in adults with ADHD, and (LogOdds= -0.12, =6.9 x 10 ), which was less abundant in ADHD. was further associated with hyperactivity/impulsivity symptoms and with inattention and hyperactivity/impulsivity (p <0.05). The literature points towards a role of these genera in inflammatory processes. Irreproducible results in the field of gut-microbiota research, due to between study heterogeneity and small sample sizes, stress the need for meta-analytic approaches and large sample sizes. While we robustly identified genera associated with adult ADHD, that might overall be considered beneficial or risk-conferring, functional studies are needed to shed light on these properties.
注意力缺陷/多动障碍（ADHD）是一种常见的神经发育疾病，大多数患者会持续到成年期。虽然肠道微生物群似乎与ADHD有关，但关于ADHD患者肠道微生物改变的少数出版物在研究的表型、测序方法/区域、预处理、统计方法和研究结果方面并不一致。为了确定成人ADHD患者肠道微生物群的改变，采用跨研究和统计方法的稳健方法，我们统一了来自四项成人ADHD病例对照研究（N = 312，N = 305）的原始16S rRNA测序数据的生物信息学流程和分析。我们研究了选定属的多样性和差异丰度（逻辑回归和类似方差分析的差异表达工具），校正了年龄和性别，并对研究结果进行了荟萃分析。对所有参与者中与多动/冲动和注意力不集中症状的关联进行了综合结果研究。尽管进行了统一分析，但β多样性与ADHD诊断相关，但队列之间存在显著异质性。有几个属与成人ADHD密切相关；例如，（对数优势=0.17，p = 4.42×10 ），在患有ADHD的成年人中更为丰富，以及（对数优势=-0.12， = 6.9×10 ），在ADHD患者中含量较低。 进一步与多动/冲动症状相关， 与注意力不集中和多动/冲动相关（p <0.05）。文献指出这些属在炎症过程中的作用。由于研究之间的异质性和样本量小，肠道微生物群研究领域的不可重复结果强调了荟萃分析方法和大样本量的必要性。虽然我们有力地确定了与成人ADHD相关的属，总体上可能被认为是有益的或具有风险的，但需要进行功能研究来阐明这些特性。
