Stiernborg Miranda, Debelius J W, Yang Liu L, Skott Elin, Millischer Vincent, Giacobini MaiBritt, Melas Philippe A, Boulund Fredrik, Lavebratt Catharina
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; The Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Brain Behav Immun. 2023 May;110:310-321. doi: 10.1016/j.bbi.2023.03.012. Epub 2023 Mar 20.
Recent evidence suggests that there is a link between neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD), and the gut microbiome. However, most studies to date have had low sample sizes, have not investigated the impact of psychostimulant medication, and have not adjusted for potential confounders, including body mass index, stool consistency and diet. To this end, we conducted the largest, to our knowledge, fecal shotgun metagenomic sequencing study in ADHD, with 147 well-characterized adult and child patients. For a subset of individuals, plasma levels of inflammatory markers and short-chain fatty acids were also measured. In adult ADHD patients (n = 84), compared to controls (n = 52), we found a significant difference in beta diversity both regarding bacterial strains (taxonomic) and bacterial genes (functional). In children with ADHD (n = 63), we found that those on psychostimulant medication (n = 33 on medication vs. n = 30 not on medication) had (i) significantly different taxonomic beta diversity, (ii) lower functional and taxonomic evenness, (iii) lower abundance of the strain Bacteroides stercoris CL09T03C01 and bacterial genes encoding an enzyme in vitamin B synthesis, and (iv) higher plasma levels of vascular inflammatory markers sICAM-1 and sVCAM-1. Our study continues to support a role for the gut microbiome in neurodevelopmental disorders and provides additional insights into the effects of psychostimulant medication. However, additional studies are needed to replicate these findings and examine causal relationships with the disorder.
近期证据表明，神经发育障碍，如注意力缺陷多动障碍（ADHD），与肠道微生物群之间存在联系。然而，迄今为止的大多数研究样本量较小，未调查精神刺激药物的影响，也未对潜在混杂因素进行调整，包括体重指数、粪便稠度和饮食。为此，据我们所知，我们对147例特征明确的成年和儿童患者进行了ADHD领域最大规模的粪便鸟枪法宏基因组测序研究。对于一部分个体，还测量了炎症标志物和短链脂肪酸的血浆水平。在成年ADHD患者（n = 84）中，与对照组（n = 52）相比，我们发现细菌菌株（分类学）和细菌基因（功能）的β多样性存在显著差异。在ADHD儿童患者（n = 63）中，我们发现服用精神刺激药物的患者（服药的n = 33，未服药的n = 30）（i）分类学β多样性显著不同，（ii）功能和分类学均匀度较低，（iii）Bacteroides stercoris CL09T03C01菌株和编码维生素B合成中一种酶的细菌基因丰度较低，以及（iv）血管炎症标志物sICAM-1和sVCAM-1的血浆水平较高。我们的研究继续支持肠道微生物群在神经发育障碍中的作用，并提供了关于精神刺激药物作用的更多见解。然而，需要更多研究来重复这些发现并检验与该疾病的因果关系。
