Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanism
Previous evidence links gut microbiota to attention-deficit/hyperactivity disorder (ADHD) through the gut-brain axis. However, the specific microbiota contributing to symptoms remain unclear. To characterize the gut microbial profile related to different symptoms and explore the mediation mechanism...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2537755 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849408312977653760 |
|---|---|
| author | Xinyue Wang Ning Wang Teng Gao Yunfan Zhang Zhao Fu Yilu Zhao Yujingwen Huang Xiangyu Zheng Xuping Gao Lin Lu Li Yang |
| author_facet | Xinyue Wang Ning Wang Teng Gao Yunfan Zhang Zhao Fu Yilu Zhao Yujingwen Huang Xiangyu Zheng Xuping Gao Lin Lu Li Yang |
| author_sort | Xinyue Wang |
| collection | DOAJ |
| description | Previous evidence links gut microbiota to attention-deficit/hyperactivity disorder (ADHD) through the gut-brain axis. However, the specific microbiota contributing to symptoms remain unclear. To characterize the gut microbial profile related to different symptoms and explore the mediation mechanism between microbiota alterations and the core ADHD symptoms, we conducted shotgun metagenomic sequencing and fecal metabolomics analysis on 94 ADHD patients and 94 age- and gender-matched controls. Microbial characteristics of three subgroups exhibiting different ADHD core symptom presentations were analyzed. We developed a metabolic model and conducted causal mediation analyses to examine how metabolites connect the microbiota to the symptoms. Fecal microbiota transplantation in mice was employed to validate the findings. The redundancy analysis identified ADHD symptoms as environmental gradients and explained the changes in beta diversity (F = 1.345, pFDR = 0.015). Greater gut microbial alterations were observed in combined presentations (ADHD-C). Several beneficial bacteria involved in short-chain fatty acid synthesis were found to be downregulated, with Lactobacillus sanfranciscensis notably linked to all three core symptoms (p.adj = 1.04E–13; p.adj = 5.07E–07; p.adj = 2.61E–05). Various taxa, functional pathways, and metabolites associated with specific ADHD symptom domains were identified. Imidazoleacetic acid partially mediated the effects between Lactobacillus sanfranciscensis and inattention (p = 0.012). In mice subjected to feces from ADHD patients with a low abundance of Lactobacillus sanfranciscensis, treatment with this strain greatly improved both hyperactivity (t = 2.665, p = 0.0237) and inattention (t = 2.389, p = 0.0380), while acetate supplementation only alleviated inattention (t = 2.362, p = 0.0398). Our findings suggest that different ADHD symptoms were related to common and different gut microbiota and metabolites. Fecal microbiota transplantation in mice validated the hypothesis that gut microbial composition affects ADHD symptoms through metabolic alterations. This study provides more insight into the mechanisms underlying metabolic disturbances in ADHD and elucidates the role of gut microbiota in these processes. |
| format | Article |
| id | doaj-art-ab4ff943c83a453b8fca865ebd7c60fd |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-ab4ff943c83a453b8fca865ebd7c60fd2025-08-20T03:35:48ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2537755Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanismXinyue Wang0Ning Wang1Teng Gao2Yunfan Zhang3Zhao Fu4Yilu Zhao5Yujingwen Huang6Xiangyu Zheng7Xuping Gao8Lin Lu9Li Yang10National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaDepartment of Medicine, Peking University, Beijing, ChinaNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaDepartment of Medicine, Peking University, Beijing, ChinaNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaNational Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, ChinaPrevious evidence links gut microbiota to attention-deficit/hyperactivity disorder (ADHD) through the gut-brain axis. However, the specific microbiota contributing to symptoms remain unclear. To characterize the gut microbial profile related to different symptoms and explore the mediation mechanism between microbiota alterations and the core ADHD symptoms, we conducted shotgun metagenomic sequencing and fecal metabolomics analysis on 94 ADHD patients and 94 age- and gender-matched controls. Microbial characteristics of three subgroups exhibiting different ADHD core symptom presentations were analyzed. We developed a metabolic model and conducted causal mediation analyses to examine how metabolites connect the microbiota to the symptoms. Fecal microbiota transplantation in mice was employed to validate the findings. The redundancy analysis identified ADHD symptoms as environmental gradients and explained the changes in beta diversity (F = 1.345, pFDR = 0.015). Greater gut microbial alterations were observed in combined presentations (ADHD-C). Several beneficial bacteria involved in short-chain fatty acid synthesis were found to be downregulated, with Lactobacillus sanfranciscensis notably linked to all three core symptoms (p.adj = 1.04E–13; p.adj = 5.07E–07; p.adj = 2.61E–05). Various taxa, functional pathways, and metabolites associated with specific ADHD symptom domains were identified. Imidazoleacetic acid partially mediated the effects between Lactobacillus sanfranciscensis and inattention (p = 0.012). In mice subjected to feces from ADHD patients with a low abundance of Lactobacillus sanfranciscensis, treatment with this strain greatly improved both hyperactivity (t = 2.665, p = 0.0237) and inattention (t = 2.389, p = 0.0380), while acetate supplementation only alleviated inattention (t = 2.362, p = 0.0398). Our findings suggest that different ADHD symptoms were related to common and different gut microbiota and metabolites. Fecal microbiota transplantation in mice validated the hypothesis that gut microbial composition affects ADHD symptoms through metabolic alterations. This study provides more insight into the mechanisms underlying metabolic disturbances in ADHD and elucidates the role of gut microbiota in these processes.https://www.tandfonline.com/doi/10.1080/19490976.2025.2537755Attention deficit hyperactivity disordermetabolitesmicrobiota-gut-brain axisfecal microbiota transplantation |
| spellingShingle | Xinyue Wang Ning Wang Teng Gao Yunfan Zhang Zhao Fu Yilu Zhao Yujingwen Huang Xiangyu Zheng Xuping Gao Lin Lu Li Yang Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanism Gut Microbes Attention deficit hyperactivity disorder metabolites microbiota-gut-brain axis fecal microbiota transplantation |
| title | Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanism |
| title_full | Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanism |
| title_fullStr | Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanism |
| title_full_unstemmed | Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanism |
| title_short | Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanism |
| title_sort | symptom specific gut microbial and metabolic profiles in adhd reveal scfa deficiency as a key pathogenic mechanism |
| topic | Attention deficit hyperactivity disorder metabolites microbiota-gut-brain axis fecal microbiota transplantation |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2537755 |
| work_keys_str_mv | AT xinyuewang symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT ningwang symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT tenggao symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT yunfanzhang symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT zhaofu symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT yiluzhao symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT yujingwenhuang symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT xiangyuzheng symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT xupinggao symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT linlu symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism AT liyang symptomspecificgutmicrobialandmetabolicprofilesinadhdrevealscfadeficiencyasakeypathogenicmechanism |