Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment.
Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment.
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ADHD 的肠道宏基因组特征揭示了与卵形拟杆菌相关的宿主认知障碍较低
DOI：
10.1080/19490976.2022.2125747
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发表时间：
2022-01
期刊：
影响因子：
12.2
通讯作者：
中科院分区：
文献类型：
--
作者：
摘要注意力缺陷多动障碍（ADHD）是一种高度异质性的精神疾病，可有三种表型表现：注意力不集中（I-ADHD）、多动冲动（HI-ADHD）和混合型（C-ADHD）。与肠道微生物群相关的环境因素与ADHD的发展有关。然而，不同的ADHD症状表现是否与不同的微生物群组成有关，以及患者是否可以从纠正异常细菌定植中获益，在很大程度上仍然不清楚。我们对207份人类粪便样本进行了宏基因组鸟枪分析，以表征根据表型表现分组的ADHD患者的肠道微生物谱。然后，我们将在患者亚组中鉴定的候选低丰度细菌移植到ADHD大鼠中，并评估这些大鼠中ADHD相关的行为和神经元激活。C-ADHD患者的肠道微生物组成与健康对照（HC）不同（p = 0.02），但与I-ADHD患者无关。八个物种逐渐减弱或丰富的HC的组成相比，那些I-ADHD和C-ADHD，特别是，丰富的卵形拟杆菌耗尽C-ADHD患者。反过来，卵形拟杆菌补充改善ADHD大鼠的空间工作记忆缺陷和逆转θ脑电图节律改变。此外，卵形拟杆菌诱导增强海马CA 1区的神经元激活。这些发现表明，当考虑更异质的患者组时，C-ADHD患者特有的肠道微生物特征可能会被掩盖。我们在ADHD动物模型中将肠道微生物群与大脑功能联系起来，这表明测试ADHD某些方面的潜在细菌干预的相关性。
ABSTRACT Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can have three phenotypical presentations: inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD). Environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota compositions and whether patients could benefit from the correction of aberrant bacterial colonization are still largely unclear. We carried out metagenomic shotgun analysis with 207 human fecal samples to characterize the gut microbial profiles of patients with ADHD grouped according to their phenotypical presentation. Then, we transplanted the candidate low-abundance bacteria identified in patient subgroups into ADHD rats and evaluated ADHD-associated behaviors and neuronal activation in these rats. Patients with C-ADHD had a different gut microbial composition from that of healthy controls (HCs) (p = .02), but not from that of I-ADHD patients. Eight species became progressively attenuated or enriched when comparing the compositions of HCs to those of I-ADHD and C-ADHD; in particular, the abundance of Bacteroides ovatus was depleted in patients with C-ADHD. In turn, Bacteroides ovatus supplementation ameliorated spatial working memory deficits and reversed θ electroencephalogram rhythm alterations in ADHD rats. In addition, Bacteroides ovatus induced enhanced neuronal activation in the hippocampal CA1 subregion. These findings indicate that gut microbial characteristics that are unique to patients with C-ADHD may be masked when considering a more heterogeneous group of patients. We link the gut microbiota to brain function in an ADHD animal model, suggesting the relevance of testing a potential bacteria-based intervention for some aspects of ADHD.
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