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      The role of the microbiota-gut-brain axis in neuropsychiatric disorders

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          Abstract

          The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson’s disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host’s immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.

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          Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.

          Colin Hill, Francisco Guarner, Gregor Reid … (2014)
          An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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            From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

            Ara Koh, Filipe De Vadder, Petia Kovatcheva-Datchary … (2016)
            A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.
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              The Microbiota-Gut-Brain Axis

              John F. Cryan, Kenneth J. O'Riordan, Caitlin S M Cowan … (2019)
              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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                Author and article information

                Journal
                Journal ID (nlm-ta): Braz J Psychiatry
                Journal ID (iso-abbrev): Braz J Psychiatry
                Journal ID (publisher-id): bjp
                Title: Brazilian Journal of Psychiatry
                Publisher: Associação Brasileira de Psiquiatria
                ISSN (Print): 1516-4446
                ISSN (Electronic): 1809-452X
                Publication date (Electronic): 10 July 2020
                Publication date Collection: May-Jun 2021
                Volume: 43
                Issue: 3
                Pages: 293-305
                Affiliations
                [1 ]Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil
                [2 ]Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
                [3 ]Department of Neurology, McGovern Medical School, UTHealth, Houston, TX, USA
                [4 ]Laboratório de Neuropsicofarmacologia, Núcleo de Pesquisa e Desenvolvimento de Medicamentos, Faculdade de Medicina, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil
                [5 ]Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Ribeirão Preto, SP, Brazil
                Author notes
                Correspondence: Tatiana Barichello, The University of Texas Health Science Center at Houston, McGovern Medical School, Faillace Department of Psychiatry and Behavioral Sciences, 1941 East Road, Suite 3140, Houston, Texas, 77054, USA. E-mail: Tatiana.Barichello@ 123456uth.tmc.edu
                Author information
                http://orcid.org/0000-0003-0571-6764
                http://orcid.org/0000-0003-3069-7139
                http://orcid.org/0000-0001-8980-9970
                http://orcid.org/0000-0001-7776-8454
                Article
                DOI: 10.1590/1516-4446-2020-0987
                PMC ID: 8136391
                PubMed ID: 32667590
                SO-VID: d10594bf-429d-4424-b3a0-ffe728cba9de
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 27 March 2020
                Date accepted : 30 April 2020
                Categories
                Subject: Special Article

                Keywords: prebiotics,probiotics,microbiota-gut-brain axis,neuroinflammation,neuropsychiatric disorders
                Data availability:
                Keywords: prebiotics, probiotics, microbiota-gut-brain axis, neuroinflammation, neuropsychiatric disorders

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