Microbiota, Immunoregulatory Old Friends and Psychiatric Disorders

  • Graham A. W. Rook
  • Charles L. Raison
  • Christopher A. Lowry
Part of the Advances in Experimental Medicine and Biology book series (AEMB, 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.

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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Copyright information

© Springer New York 2014

Authors and Affiliations

  • Graham A. W. Rook
    • 1
  • Charles L. Raison
    • 2
  • Christopher A. Lowry
    • 3
  1. 1.Centre for Clinical MicrobiologyUCL (University College London)LondonUK
  2. 2.Department of Psychiatry, College of Medicine and Norton School of Family and Consumer Sciences, College of Agriculture and Life SciencesUniversity of ArizonaTucsonUSA
  3. 3.Department of Integrative Physiology and Center for NeuroscienceUniversity of Colorado BoulderBoulderUSA

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