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      The Gut Microbiome in Schizophrenia and the Potential Benefits of Prebiotic and Probiotic Treatment

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          Abstract

          The gut microbiome (GMB) plays an important role in developmental processes and has been implicated in the etiology of psychiatric disorders. However, the relationship between GMB and schizophrenia remains unclear. In this article, we review the existing evidence surrounding the gut microbiome in schizophrenia and the potential for antipsychotics to cause adverse metabolic events by altering the gut microbiome. We also evaluate the current evidence for the clinical use of probiotic and prebiotic treatment in schizophrenia. The current data on microbiome alteration in schizophrenia remain conflicting. Longitudinal and larger studies will help elucidate the confounding effect on the microbiome. Current studies help lay the groundwork for further investigations into the role of the GMB in the development, presentation, progression and potential treatment of schizophrenia.

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          Host microbiota constantly control maturation and function of microglia in the CNS.

          Daniel Erny, Anna de Angelis, Diego Jaitin … (2015)
          As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.
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            Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.

            Jessica M. Yano, Kristie Yu, Gregory P. Donaldson … (2015)
            The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biological processes.
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              Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.

              J A Bravo, P Forsythe, M. V. Chew … (2011)
              There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA(Aα2) mRNA expression in the prefrontal cortex and amygdala, but increased GABA(Aα2) in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.
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                Author and article information

                Contributors
                Isabel Goñi: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Nutrients
                Journal ID (iso-abbrev): Nutrients
                Journal ID (publisher-id): nutrients
                Title: Nutrients
                Publisher: MDPI
                ISSN (Electronic): 2072-6643
                Publication date (Electronic): 31 March 2021
                Publication date Collection: April 2021
                Volume: 13
                Issue: 4
                Electronic Location Identifier: 1152
                Affiliations
                [1 ]Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON M5T 1R8, Canada; jonathan.liu@ 123456camh.ca (J.C.W.L.); ilona.gorbovskaya@ 123456camh.ca (I.G.); margaret.hahn@ 123456camh.ca (M.K.H.)
                [2 ]Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada
                [3 ]Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada
                [4 ]Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
                [5 ]Banting and Best Diabetes Centre, University of Toronto, ON M5G 2C4, Canada
                Author notes
                Author information
                https://orcid.org/0000-0002-6093-7562
                Article
                Publisher ID: nutrients-13-01152
                DOI: 10.3390/nu13041152
                PMC ID: 8065775
                PubMed ID: 33807241
                SO-VID: 1c60c39d-7ce1-4b69-803c-1177d0eb0f2c
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 22 February 2021
                Date accepted : 27 March 2021
                Categories
                Subject: Review

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: gut microbiome,gut–brain axis,schizophrenia,antipsychotics,prebiotics,probiotics,psychobiotics
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: gut microbiome, gut–brain axis, schizophrenia, antipsychotics, prebiotics, probiotics, psychobiotics

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