Elsevier

Pathologie Biologie

Volume 63, Issue 1, February 2015, Pages 35-42
Pathologie Biologie

Review
The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: A systematic reviewLe microbiote intestinal : un rôle potentiel dans les troubles psychiatriques majeurs

https://doi.org/10.1016/j.patbio.2014.10.003Get rights and content

Abstract

The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.

Résumé

Le microbiote intestinal est considéré de plus en plus comme un partenaire symbiotique contribuant au bon état de santé général de l’organisme. Les approches métagénomiques, en pleine expansion, permettent de mieux en mieux appréhender la complexité de l’écosystème intestinal et de son impact sur le développement et le fonctionnement du système nerveux central de son hôte. Elles pourraient permettre à l’avenir le développement de thérapeutiques spécifiques ciblant le microbiote intestinal, comme les probiotiques, les prébiotiques et les approches nutritionnelles chez les patients souffrant de troubles mentaux. Ces traitements existent déjà dans le traitement de certaines pathologies intestinales, mais l’efficacité, le type de souches, la quantité et la durée administrée restent à déterminer chez l’humain, alors que les résultats animaux sont très prometteurs dans les modèles de troubles anxieux et de stress chronique. Le but de la présente revue est de synthétiser les données actuelles, d’une part, sur l’association entre la dysbiose du microbiote intestinal et le déclenchement ou l’entretien de troubles psychiatriques, et d’autre part, d’explorer les thérapeutiques potentielles qui pourraient être proposées aux patients souffrant de troubles psychiatriques associés à une dysbiose intestinale.

Introduction

Mood and anxiety disorders, schizophrenia and other mental, neurological and substance-use (MNS) disorders represent 13% of the global burden of disease [1]. While forecasts predict an increase in the prevalence of mental health disorders in the worldwide general population, the response rate to classical psychiatric treatment remains unsatisfactory. Resistance to psychotropic drugs can be due to clinical, pharmacological, pharmacokinetic, and pharmacodynamic factors. Among these factors, recent animal findings suggest that microbiota may have an underestimated influence on its host's behavior and on drug metabolism that may explain ineffectiveness or increased side-effects of psychiatric medications such as weight gain [2].

Microbiota refers to the set of microorganisms that live in a specific environment. The human gastrointestinal tract harbors a microbiota of over 1014 bacteria (mostly anaerobic), yeasts, fungi and viruses [3], which means that there are 10 times more prokaryotic cells than eukaryotic cells in the human organism.

Figures are even more impressive from the genes’ perspective; it is estimated that the intestinal “microbiome”, i.e. the collective gene repertoire of the organisms comprising the gut microbiota, contains well over 150 times more unique genes than the human genome [4]. The role of microbiota has been underestimated until recent years and could be of major importance in regulating multiple vital functions of the body.

The human microbiota composition is host-specific, relatively stable in short time [5]. The microbiome is mainly composed of two bacterial phyla, Bacteroidetes and Firmicutes, other such as Proteobacteria, Actinobacteria, Fusobacteria, Archaea and Verrucomicrobia phyla are also present but in relatively small quantities [6]. Microbiota matures in the first three years of life [7] and has a physiological fundamental role in intestinal motility and in the development of the metabolic and immune systems (mucosal and systemic) [8], thus protecting the host against pathogens, participating in the digestion of meals and drugs, and influencing fat absorption and distribution [2], [9], [10]. Hosts also benefit from several other properties of the intestinal microbiota: vitamin K synthesis, trophic effects on intestinal epithelial cells, energy salvaging from unabsorbed food by short-chain fatty acids (SCFA) production, growth inhibition of pathogens, maintenance of the intestinal barrier integrity and mucosal immune homeostasis and participation in the xenobiotic metabolism system [11].

Several excellent recent reviews summarized fundamental data on microbiota's influence on the central nervous system, based mainly on in vitro and animal studies and, in humans, on inflammatory bowel disorders [12], [13]. The objective of the present article was to summarize the current data on microbiota's potential role in psychiatric disorder genesis and/or maintenance, and to explore the potential new therapeutic opportunities targeting microbiota's dysbiosis in psychiatric disorders.

Section snippets

Search strategy

Although the present review is a narrative review, due to the lack of data and the paucity of studies in humans, the present work was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement [14]. PubMed (from 1966 to September 2013), Embase (from 1980 to September 2013), PsychINFO (from 1806 to September 2013), BIOSIS (from 1926 to September 2013), Science Direct (from 2006 to September 2013), and Cochrane CENTRAL (from 1993 to September 2013) were

Results

Overall, 1089 abstracts were screened of which 183 articles that studied the association between gut microbiota and central nervous system functioning or psychiatric disorders were included in the present review. The following issues were identified:

  • microbiota dysbiosis and putative consequences on central nervous system functioning;

  • chronic microbiota dysbiosis-associated illnesses in humans;

  • microbiota-oriented treatments and their potential therapeutic applications in psychiatry.

Conclusion

Research on the role of the human intestinal microbiota in the genesis and/or maintenance of psychiatric disorders is in its infancy but appears as one of the most promising avenues of research in psychiatry. While rodent models suggest that the microbiota plays a fundamental role in the genesis of the HPA axis, the serotoninergic system and the immuno-inflammatory system, and that the microbiota can affect the CNS through multiple pathways, few studies have been carried out on humans. Today,

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Funding: No funding source.

Acknowledgements

This work was supported by Inserm, Assistance publique–Hôpitaux de Paris, RTRS santé mentale (fondation fondamentale) and by Agence nationale pour la recherche (ANR: NEURO 2009, V.I.P. project). This work was supported (in part) by the Investissements d’Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02.

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    1

    G.F. and W.B. equally contributed to the writing of the article.

    2

    M.L. and R.T. equally directed the writing of the article.

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