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Microbiota, Immunoregulatory Old Friends and Psychiatric Disorders

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Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((MICENDO,volume 817))

Abstract

Regulation of the immune system is an important function of the gut microbiota. Increasing evidence suggests that modern living conditions cause the gut microbiota to deviate from the form it took during human evolution. Contributing factors include loss of helminth infections, encountering less microbial biodiversity, and modulation of the microbiota composition by diet and antibiotic use. Thus the gut microbiota is a major mediator of the hygiene hypothesis (or as we prefer, “Old Friends” mechanism), which describes the role of organisms with which we co-evolved, and that needed to be tolerated, as crucial inducers of immunoregulation. At least partly as a consequence of reduced exposure to immunoregulatory Old Friends, many but not all of which resided in the gut, high-income countries are undergoing large increases in a wide range of chronic inflammatory disorders including allergies, autoimmunity and inflammatory bowel diseases. Depression, anxiety and reduced stress resilience are comorbid with these conditions, or can occur in individuals with persistently raised circulating levels of biomarkers of inflammation in the absence of clinically apparent peripheral inflammatory disease. Moreover poorly regulated inflammation during pregnancy might contribute to brain developmental abnormalities that underlie some cases of autism spectrum disorders and schizophrenia. In this chapter we explain how the gut microbiota drives immunoregulation, how faulty immunoregulation and inflammation predispose to psychiatric disease, and how psychological stress drives further inflammation via pathways that involve the gut and microbiota. We also outline how this two-way relationship between the brain and inflammation implicates the microbiota, Old Friends and immunoregulation in the control of stress resilience.

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Abbreviations

ASD:

Autism spectrum disorders

BH4:

Tetrahydrobiopterin

CD:

Crohn’s disease

CNS:

Central nervous system

CRH:

Corticotropin-releasing hormone

CRP:

C-reactive protein

dACC:

Dorsal anterior cingulate cortex

DC:

Dendritic cells

DCreg:

Regulatory dendritic cells

fMRI:

Functional magnetic resonance imaging

GABA:

g-Aminobutyric acid

GCR:

Glucocorticoid resistance

HPA:

Hypothalamic-pituitary adrenal axis

IBD:

Inflammatory bowel disease

IBS:

Irritable bowel syndrome

IDO:

Indoleamine-2,3-dioxygenase

IFN-α:

Interferon-alpha

IL:

Interleukin

LPS:

Lipopolysaccharide

MCP-1:

Monocyte chemoattractant protein-1

MS:

Multiple sclerosis

NO:

Nitric oxide

Nod1:

Nucleotide-binding oligomerization domain-containing protein-1

PBMCs:

Peripheral blood monocyte cells

PET:

Positron emission tomography

SCFA:

Short chain fatty acids

SLE:

Systemic lupus erythematosus

SNP:

Single nucleotide polymorphisms

SNS:

Sympathetic nervous system

SSRI:

Selective serotonin reuptake inhibitors

T1D:

Type 1 diabetes

TNF:

Tumor necrosis factor

Treg:

Regulatory T cells

UC:

Ulcerative colitis

XLAAD:

X-linked autoimmunity-allergic dysregulation syndrome

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Acknowledgements

GAWR is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. CLR receives grant support from the National Center for Complementary and Alternative Medicine (R01AT004698, R01AT004698-01A1S1), the Depressive and Bipolar Disorder Alternative Treatment Foundation and The Brain and Behavior Research Foundation. He reports the following activities for the previous 2 years: advisory board participation and related travel funds for Pamlab, Lilly and North American Center for Continuing Education; development and presentation of disease state slides for Pamlab, Pfizer and Johnson & Johnson, as well as related travel funds for these activities; development of continuing medical education material for North American Center for Continuing Education and for CME Incite. CAL receives grant support from the National Institute of Mental Health (R01MH065702, R01MH086539, R01DA019921, R01MH075968), the National Science Foundation (NSF- IOS 0921969), the Depressive and Bipolar Disorder Alternative Treatment Foundation, and is the recipient of an NSF CAREER Award (NSF-IOS 0845550) and a NARSAD, Brain & Behavior Research Foundation 2010 Young Investigator Award. He reports the following activities for the previous 2 years: consultant for Enlight Biosciences.

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Authors and Affiliations

  1. Centre for Clinical Microbiology, UCL (University College London), Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK

    Graham A. W. Rook

  2. Department of Psychiatry, College of Medicine and Norton School of Family and Consumer Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ, USA

    Charles L. Raison

  3. Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA

    Christopher A. Lowry

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  1. Graham A. W. Rook
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  2. Charles L. Raison
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  3. Christopher A. Lowry
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Correspondence to Graham A. W. Rook .

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Editors and Affiliations

  1. Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center, Abilene, Texas, USA

    Mark Lyte

  2. Department of Anatomy and Neuroscience, University College, Cork, Cork, Ireland

    John F. Cryan

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Rook, G.A.W., Raison, C.L., Lowry, C.A. (2014). Microbiota, Immunoregulatory Old Friends and Psychiatric Disorders. In: Lyte, M., Cryan, J. (eds) Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease. Advances in Experimental Medicine and Biology(), vol 817. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0897-4_15

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