Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome
The extra copy of the methyl-CpG-binding protein 2 (MeCp2) gene causes MeCP2 duplication syndrome (MDS), a neurodevelopmental disorder characterized by intellectual disability and autistic phenotypes. However, the disturbed microbiome and metabolic profiling underlying the autistic-like behavioral d...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923023002873 |
| _version_ | 1827394839132504064 |
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| author | Junfang Wu Qingyu Hu Xiaoping Rao Hongyang Zhao Huiru Tang Yulan Wang |
| author_facet | Junfang Wu Qingyu Hu Xiaoping Rao Hongyang Zhao Huiru Tang Yulan Wang |
| author_sort | Junfang Wu |
| collection | DOAJ |
| description | The extra copy of the methyl-CpG-binding protein 2 (MeCp2) gene causes MeCP2 duplication syndrome (MDS), a neurodevelopmental disorder characterized by intellectual disability and autistic phenotypes. However, the disturbed microbiome and metabolic profiling underlying the autistic-like behavioral deficits of MDS are rarely investigated. Here we aimed to understand the contributions of microbiome disruption and associated metabolic alterations, especially the disturbed neurotransmitters in MDS employing a transgenic mouse model with MeCP2 overexpression. We analyzed metabolic profiles of plasma, urine, and cecum content and microbiome profiles by both 16 s RNA and shotgun metagenomics sequence technology. We found the decreased levels of Firmicutes and increased levels of Bacteroides in the single MeCP2 gene mutation autism-like mouse model, demonstrating the importance of the host genome in a selection of microbiome, leading to the heterogeneity characteristics of microbiome in MDS. Furthermore, the changed levels of several neurotransmitters (such as dopamine, taurine, and glutamate) implied the excitatory-inhibitory imbalance caused by the single gene mutation. Concurrently, a range of microbial metabolisms of aromatic amino acids (such as tryptophan and phenylalanine) were identified in different biological matrices obtained from MeCP2 transgenic mice. Our investigation revealed the importance of genetic variation in accounting for the differences in microbiomes and confirmed the bidirectional regulatory axis of microbiota-gut-brain in studying the role of microbiome on MDS, which could be useful in deeply understanding the microbiome-based treatment in this autistic-like disease. |
| first_indexed | 2024-03-08T18:20:00Z |
| format | Article |
| id | doaj.art-c70a216863c14614997cab114691fd5d |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-08T18:20:00Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-c70a216863c14614997cab114691fd5d2023-12-31T04:25:57ZengElsevierBrain Research Bulletin1873-27472024-01-01206110862Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndromeJunfang Wu0Qingyu Hu1Xiaoping Rao2Hongyang Zhao3Huiru Tang4Yulan Wang5Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430000, China; Corresponding authors.State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaState Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430000, ChinaDepartment of Pediatrics, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaSingapore Phenome Center, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore; Corresponding authors.The extra copy of the methyl-CpG-binding protein 2 (MeCp2) gene causes MeCP2 duplication syndrome (MDS), a neurodevelopmental disorder characterized by intellectual disability and autistic phenotypes. However, the disturbed microbiome and metabolic profiling underlying the autistic-like behavioral deficits of MDS are rarely investigated. Here we aimed to understand the contributions of microbiome disruption and associated metabolic alterations, especially the disturbed neurotransmitters in MDS employing a transgenic mouse model with MeCP2 overexpression. We analyzed metabolic profiles of plasma, urine, and cecum content and microbiome profiles by both 16 s RNA and shotgun metagenomics sequence technology. We found the decreased levels of Firmicutes and increased levels of Bacteroides in the single MeCP2 gene mutation autism-like mouse model, demonstrating the importance of the host genome in a selection of microbiome, leading to the heterogeneity characteristics of microbiome in MDS. Furthermore, the changed levels of several neurotransmitters (such as dopamine, taurine, and glutamate) implied the excitatory-inhibitory imbalance caused by the single gene mutation. Concurrently, a range of microbial metabolisms of aromatic amino acids (such as tryptophan and phenylalanine) were identified in different biological matrices obtained from MeCP2 transgenic mice. Our investigation revealed the importance of genetic variation in accounting for the differences in microbiomes and confirmed the bidirectional regulatory axis of microbiota-gut-brain in studying the role of microbiome on MDS, which could be useful in deeply understanding the microbiome-based treatment in this autistic-like disease.http://www.sciencedirect.com/science/article/pii/S0361923023002873MetabolicMicrobiomeMeCP2 duplication syndromeAutism spectrum disorderGene variation |
| spellingShingle | Junfang Wu Qingyu Hu Xiaoping Rao Hongyang Zhao Huiru Tang Yulan Wang Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome Brain Research Bulletin Metabolic Microbiome MeCP2 duplication syndrome Autism spectrum disorder Gene variation |
| title | Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome |
| title_full | Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome |
| title_fullStr | Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome |
| title_full_unstemmed | Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome |
| title_short | Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome |
| title_sort | gut microbiome and metabolic profiles of mouse model for mecp2 duplication syndrome |
| topic | Metabolic Microbiome MeCP2 duplication syndrome Autism spectrum disorder Gene variation |
| url | http://www.sciencedirect.com/science/article/pii/S0361923023002873 |
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