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      Washed Microbiota Transplantation Accelerates the Recovery of Abnormal Changes by Light-Induced Stress in Tree Shrews

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          Abstract

          The gut and brain interact constantly in a complex fashion. Its intricacy and intrigue is progressively being revealed in the study of the “gut–brain axis”. Among many factors, abnormal light exposure is a potential powerful stressor, which is becoming ever more pervasive in our modern society. However, little is known about how stress, induced by staying up late by light, affects the gut–brain axis. We addressed this question by extending the normal circadian light for four hours at night in fifteen male tree shrews to simulate the pattern of staying up late in humans. The behavior, biochemical tests, microbiota dynamics, and brain structure of tree shrews were evaluated. The simple prolongation of light in the environment resulted in substantial changes of body weight loss, behavioral differences, total sleep time reduction, and an increased level of urine cortisol. These alterations were rescued by the treatment of either ketamine or washed microbiota transplantation (WMT). Importantly, the sustainability of WMT effect was better than that of ketamine. Magnetic Resonance Imaging analysis indicated that ketamine acted on the hippocampus and thalamus, and WMT mainly affected the piriform cortex and lateral geniculate nucleus. In conclusion, long-term light stimulation could change the behaviors, composition of gut microbiota and brain structure in tree shrews. Targeting microbiota thus certainly holds promise as a treatment for neuropsychiatric disorders, including but not limited to stress-related diseases.

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          Most cited references53

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          The Microbiota-Gut-Brain Axis

          The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. 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.
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            Unified segmentation.

            A probabilistic framework is presented that enables image registration, tissue classification, and bias correction to be combined within the same generative model. A derivation of a log-likelihood objective function for the unified model is provided. The model is based on a mixture of Gaussians and is extended to incorporate a smooth intensity variation and nonlinear registration with tissue probability maps. A strategy for optimising the model parameters is described, along with the requisite partial derivatives of the objective function.
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              Voxel-based morphometry--the methods.

              At its simplest, voxel-based morphometry (VBM) involves a voxel-wise comparison of the local concentration of gray matter between two groups of subjects. The procedure is relatively straightforward and involves spatially normalizing high-resolution images from all the subjects in the study into the same stereotactic space. This is followed by segmenting the gray matter from the spatially normalized images and smoothing the gray-matter segments. Voxel-wise parametric statistical tests which compare the smoothed gray-matter images from the two groups are performed. Corrections for multiple comparisons are made using the theory of Gaussian random fields. This paper describes the steps involved in VBM, with particular emphasis on segmenting gray matter from MR images with nonuniformity artifact. We provide evaluations of the assumptions that underpin the method, including the accuracy of the segmentation and the assumptions made about the statistical distribution of the data. Copyright 2000 Academic Press.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                23 June 2021
                2021
                : 11
                : 685019
                Affiliations
                [1] 1 Department of Neurobiology, School of Basic Medical Sciences, Nanjing Medical University , Nanjing, China
                [2] 2 Visual Cognition Laboratory, Department of Medicine, University of Fribourg , Fribourg, Switzerland
                [3] 3 Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University , Nanjing, China
                [4] 4 Key Lab of Holistic Integrative Enterology, Nanjing Medical University , Nanjing, China
                [5] 5 PET Center, Huashan Hospital, Fudan University , Shanghai, China
                [6] 6 Animal Core Facility of Nanjing Medical University, Nanjing Medical University , Nanjing, China
                [7] 7 Department of Rehabilitation Medicine, Jiangsu Shengze Hospital Affiliated to Nanjing Medical University, Nanjing Medical University , Nanjing, China
                Author notes

                Edited by: Tingtao Chen, Nanchang University, China

                Reviewed by: Hailong Cao, Tianjin Medical University General Hospital, China; Gang Wang, Jiangnan University, China

                *Correspondence: Jun Gao, gaojun@ 123456njmu.edu.cn ; Faming Zhang, fzhang@ 123456njmu.edu.cn

                This article was submitted to Microbiome in Health and Disease, a section of the journal Frontiers in Cellular and Infection Microbiology

                †These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fcimb.2021.685019
                8262326
                f7a0cf56-f70d-4228-90a9-8ebc384f402c
                Copyright © 2021 Wang, Li, Huang, Lv, Li, Dai, Zhou, Xu, Zhang and Gao

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 March 2021
                : 21 May 2021
                Page count
                Figures: 5, Tables: 3, Equations: 0, References: 53, Pages: 14, Words: 6749
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                gut–brain axis,staying up late,stress,tree shrew,magnetic resonance imaging,washed microbiota transplantation

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