Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment
Yan Li,
Haiting Sun,
Yufen Huang,
Anqi Yin,
Linjuan Zhang,
Jiao Han,
Yixuan Lyu,
Xiangzhao Xu,
Yifang Zhai,
Huan Sun,
Ping Wang,
Jinyang Zhao,
Silong Sun,
Hailong Dong,
Feng Zhu,
Qiang Wang,
Luis Augusto Rohde,
Xuefeng Xie,
Xin Sun,
Lize Xiong
Affiliations
Yan Li
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Haiting Sun
Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University, Xi’an, China
Yufen Huang
BGI-Shenzhen, Shenzhen, China
Anqi Yin
Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, Xi’an, China
Linjuan Zhang
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Jiao Han
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Yixuan Lyu
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Xiangzhao Xu
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Yifang Zhai
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Huan Sun
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Ping Wang
Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University, Xi’an, China
Jinyang Zhao
BGI-Shenzhen, Shenzhen, China
Silong Sun
BGI-Shenzhen, Shenzhen, China
Hailong Dong
Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, Xi’an, China
Feng Zhu
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Qiang Wang
Department of Anesthesiology and Perioperative Medicine & Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Luis Augusto Rohde
ADHD and Developmental Psychiatry Programs, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil
Xuefeng Xie
BGI-Sanya, Sanya, China
Xin Sun
Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University, Xi’an, China
Lize Xiong
Translational Research Institute of Brain and Brain-Like Intelligence & Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
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.
