title: Hygiene and other early childhood influences on the subsequent function of the immune system.
abstract: The immune system influences brain development and function. Hygiene and other early childhood influences impact the subsequent function of the immune system during adulthood, with consequences for vulnerability to neurodevelopmental and psychiatric disorders. Inflammatory events during pregnancy can act directly to cause developmental problems in the central nervous system (CNS) that have been implicated in schizophrenia and autism. The immune system also acts indirectly by "farming" the intestinal microbiota, which then influences brain development and function via the multiple pathways that constitute the gut-brain axis. The gut microbiota also regulates the immune system. Regulation of the immune system is crucial because inflammatory states in pregnancy need to be limited, and throughout life inflammation needs to be terminated completely when not required; for example, persistently raised levels of background inflammation during adulthood (in the presence or absence of a clinically apparent inflammatory stimulus) correlate with an increased risk of depression. A number of factors in the perinatal period, notably immigration from rural low-income to rich developed settings, caesarean delivery, breastfeeding and antibiotic abuse have profound effects on the microbiota and on immunoregulation during early life that persist into adulthood. Many aspects of the modern western environment deprive the infant of the immunoregulatory organisms with which humans co-evolved, while encouraging exposure to non-immunoregulatory organisms, associated with more recently evolved "crowd" infections. Finally, there are complex interactions between perinatal psychosocial stressors, the microbiota, and the immune system that have significant additional effects on both physical and psychiatric wellbeing in subsequent adulthood. This article is part of a Special Issue entitled Neuroimmunology in Health And Disease.
authors.affiliation: Centre for Clinical Microbiology, Department of Infection, University College London (UCL), London, UK. Electronic address: g.rook@ucl.ac.uk.
authors.forename: Graham A W
authors.initials: GA
authors.lastname: Rook
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
authors.affiliation: 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.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Raison
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000254:growth & development / Q000276:immunology*; D002648:Child; D005260:Female; D047109:Fetal Development / Q000276:immunology; D006801:Humans; D006920:Hygiene; D007107:Immune System / Q000254:growth & development* / Q000276:immunology*; D007154:Immune System Diseases / Q000209:etiology; D007249:Inflammation / Q000276:immunology; D008019:Life Style; D001523:Mental Disorders / Q000276:immunology; D064307:Microbiota / Q000276:immunology; D011247:Pregnancy; D012959:Socioeconomic Factors; D013315:Stress, Psychological / Q000276:immunology
keywords: Co-evolution; Depression; Hygiene; Immunoregulation; Microbiota; Old Friends