Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice.
Anouk C. Tengeler,Sarita A. Dam,Maximilian Wiesmann,Jilly Naaijen,Miranda van Bodegom,Clara Belzer,Pieter J. Dederen,Vivienne Verweij,Barbara Franke,Tamas Kozicz,Tamas Kozicz,Alejandro Arias Vasquez,Amanda J. Kiliaan +12 more
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TLDR
It is demonstrated that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals’ behavior and may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders.Abstract:
The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging (MRI), and studied mouse behavior in a behavioral test battery. Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test. Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals’ behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders.read more
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Gut microbial molecules in behavioural and neurodegenerative conditions.
TL;DR: Bacterial metabolites with known or suspected neuromodulatory activity are described, mechanisms of signalling pathways from the gut microbiota to the brain are defined and direct effects that gut bacterial molecules are likely exerting on specific brain cells are discussed.
Journal ArticleDOI
Investigating the Gut Microbiota Composition of Individuals with Attention-Deficit/Hyperactivity Disorder and Association with Symptoms.
Joanna Szopinska-Tokov,Sarita Dam,Jilly Naaijen,Prokopis Konstanti,Nanda Rommelse,Clara Belzer,Jan K. Buitelaar,Barbara Franke,Esther Aarts,Alejandro Arias Vasquez +9 more
TL;DR: Variation of a genus from the Ruminococcaceae family is associated (after multiple testing correction) with inattention symptoms and support the potential role of gut microbiota in ADHD pathophysiology.
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Three Pillars of Automated Home-Cage Phenotyping of Mice: Novel Findings, Refinement, and Reproducibility Based on Literature and Experience.
Vootele Voikar,Stefano Gaburro +1 more
TL;DR: It is discussed how the integration of telemetry systems for deriving certain physiological parameters can help to complement the description of the animal model to offer better translation to human studies and how such HCM data can be statistically interpreted and analyzed.
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What Does Immunology Have to Do With Normal Brain Development and the Pathophysiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders
TL;DR: The past decade's literature is reviewed and a critical commentary on the involvement of immunological mechanisms in normal brain development, as well as its role in the pathophysiology of Tourette syndrome, other Chronic tic disorders, and related neuropsychiatric disorders including Obsessive-compulsive disorder (OCD) and Attention deficit hyperactivity disorder (ADHD).
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The gut microbiome is associated with brain structure and function in schizophrenia
Shijia Li,Jie Song,Pengfei Ke,Lingyin Kong,Bingye Lei,Jing Zhou,Yuanyuan Huang,Hehua Li,G. Y. Li,Jun Chen,Xiaobo Li,Zhiming Xiang,Yuping Ning,Fengchun Wu,Kai Wu +14 more
TL;DR: The results suggest that the potential role of the gut microbiome in SZ is related to alterations in brain structure and function, and provides insights into the underlying neuropathology of SZ.
References
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Journal ArticleDOI
Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders
Elaine Y. Hsiao,Sara Mcbride,Sophia Hsien,Gil Sharon,Embriette R. Hyde,Tyler McCue,Julian A. Codelli,Janet Chow,Sarah E. Reisman,Joseph F. Petrosino,Paul H. Patterson,Sarkis K. Mazmanian +11 more
TL;DR: A gut-microbiome-brain connection in a mouse model of ASD is supported and a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders is identified.
Journal ArticleDOI
Normal gut microbiota modulates brain development and behavior
Rochellys Diaz Heijtz,Shugui Wang,Farhana Anuar,Yu Qian,Britta Björkholm,Annika Samuelsson,Martin L. Hibberd,Hans Forssberg,Sven Pettersson +8 more
TL;DR: It is demonstrated that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota, suggesting that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
Journal ArticleDOI
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Koji Atarashi,Takeshi Tanoue,Kenshiro Oshima,Wataru Suda,Yuji Nagano,Hiroyoshi Nishikawa,Shinji Fukuda,Takuro Saito,Seiko Narushima,Koji Hase,Sangwan Kim,Joëlle V. Fritz,Paul Wilmes,Satoshi Ueha,Kouji Matsushima,Hiroshi Ohno,Bernat Olle,Shimon Sakaguchi,Tadatsugu Taniguchi,Hidetoshi Morita,Masahira Hattori,Kenya Honda +21 more
TL;DR: Using a rational approach to isolate CD4+FOXP3+ regulatory T (Treg)-cell-inducing bacterial strains from the human indigenous microbiota may allow for tailored therapeutic manipulation of human immune disorders.
Journal ArticleDOI
The Microbiota-Gut-Brain Axis
John F. Cryan,Kenneth J. O’Riordan,Caitlin S. M. Cowan,Kiran V. Sandhu,Thomaz F.S. Bastiaanssen,Marcus Boehme,Martín Gabriel Codagnone,Sofia Cussotto,Christine Fülling,Anna V. Golubeva,Katherine E. Guzzetta,Minal Jaggar,Caitriona M. Long-Smith,Joshua M. Lyte,Jason A. Martin,Alicia Molinero-Perez,Gerard M. Moloney,Emanuela Morelli,Enrique Morillas,Rory C. O'Connor,Joana S Cruz-Pereira,Veronica L. Peterson,Kieran Rea,Nathaniel L. Ritz,Eoin Sherwin,Simon Spichak,Emily M. Teichman,Marcel van de Wouw,Ana Paula Ventura-Silva,Shauna E. Wallace-Fitzsimons,Niall P. Hyland,Gerard Clarke,Timothy G. Dinan +32 more
TL;DR: Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
Journal ArticleDOI
Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity
Janet Markle,Daniel N. Frank,Steven M. Mortin-Toth,Charles E. Robertson,Leah M. Feazel,Ulrike Rolle-Kampczyk,Martin von Bergen,Kathy D. McCoy,Andrew J. Macpherson,Jayne S. Danska +9 more
TL;DR: It is demonstrated that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), and Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D.
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