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      From Maternal Diet to Neurodevelopmental Disorders: A Story of Neuroinflammation

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          Abstract

          Providing the appropriate quantity and quality of food needed for both the mother’s well-being and the healthy development of the offspring is crucial during pregnancy. However, the macro- and micronutrient intake also impacts the body’s regulatory supersystems of the mother, such as the immune, endocrine, and nervous systems, which ultimately influence the overall development of the offspring. Of particular importance is the association between unhealthy maternal diet and neurodevelopmental disorders in the offspring. Epidemiological studies have linked neurodevelopmental disorders like autism spectrum disorders, attention-deficit-hyperactivity disorder, and schizophrenia, to maternal immune activation (MIA) during gestation. While the deleterious consequences of diet-induced MIA on offspring neurodevelopment are increasingly revealed, neuroinflammation is emerging as a key underlying mechanism. In this review, we compile the evidence available on how the mother and offspring are both impacted by maternal dietary imbalance. We specifically explore the various inflammatory and anti-inflammatory effects of dietary components and discuss how changes in inflammatory status can prime the offspring brain development toward neurodevelopmental disorders. Lastly, we discuss research evidence on the mechanisms that sustain the relationship between maternal dietary imbalance and offspring brain development, involving altered neuroinflammatory status in the offspring, as well as genetic to cellular programming notably of microglia, and the evidence that the gut microbiome may act as a key mediator.

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          Microbial ecology: human gut microbes associated with obesity.

          Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.
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            The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

            Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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              What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases

              Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.
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                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                15 January 2021
                2020
                : 14
                : 612705
                Affiliations
                [1] 1Integrated Program in Neuroscience, McGill University , Montréal, QC, Canada
                [2] 2Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval , Québec, QC, Canada
                [3] 3Department of Neurosciences, University of California, San Diego , La Jolla, CA, United States
                [4] 4Cerebral Imaging Centre, Douglas Mental Health University, McGill University , Montréal, QC, Canada
                [5] 5Department of Psychiatry, McGill University , Montréal, QC, Canada
                [6] 6Department of Biological and Biomedical Engineering, McGill University , Montréal, QC, Canada
                [7] 7Département de Médecine Moléculaire, Université Laval , Québec, QC, Canada
                [8] 8Department of Neurology and Neurosurgery, McGill University , Montréal, QC, Canada
                [9] 9Division of Medical Sciences, University of Victoria , Victoria, BC, Canada
                [10] 10Biochemistry and Molecular Biology, Faculty of Medicine, The University of British Columbia , Vancouver, BC, Canada
                Author notes

                Edited by: Arumugam R. Jayakumar, Miami VA Healthcare System, United States

                Reviewed by: Kempuraj Duraisamy, University of Missouri, United States; David A. Menassa, University of Southampton, United Kingdom; Chima Ndubizu, University of Miami, United States

                *Correspondence: Marie-Ève Tremblay, evetremblay@ 123456uvic.ca

                This article was submitted to Non-Neuronal Cells, a section of the journal Frontiers in Cellular Neuroscience

                Article
                10.3389/fncel.2020.612705
                7849357
                33536875
                65f6cbbf-6f89-4793-ac60-f26734af478f
                Copyright © 2021 Bordeleau, Fernández de Cossío, Chakravarty and Tremblay.

                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
                : 30 September 2020
                : 07 December 2020
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 286, Pages: 22, Words: 0
                Funding
                Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
                Categories
                Neuroscience
                Review

                Neurosciences
                maternal diet,nutrient imbalance,inflammation,genetic programming,microglia,gut microbiome,neurodevelopmental disorders,schizophrenia

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