Hygiene and Other Early Childhood Influences on the Subsequent Function of the Immune System
Open Access
- 1 July 2011
- journal article
- review article
- Published by S. Karger AG in Digestive Diseases
- Vol. 29 (2), 144-153
- https://doi.org/10.1159/000323877
Abstract
The current 'Darwinian' synthesis of the hygiene (or 'Old Friends') hypothesis suggests that the increase in chronic inflammatory disorders that started in Europe in the mid-19th century and progressed until the late 20th century is at least partly attributable to immunodysregulation resulting from lack of exposure to microorganisms that were tasked by co-evolutionary processes with establishing the 'normal' background levels of immunoregulation, a role that they perform in concert with the normal microbiota. This is an example of 'evolved dependence'. The relevant organisms co-evolved with mammals, already accompanied early hominids in the Paleolithic era and are associated with animals, mud and faeces. These organisms often establish stable carrier states, or are encountered continuously in primitive environments as 'pseudocommensals' from mud and water. These organisms were not lost during the first epidemiological transition, which might even have resulted in increased exposure to them. However, the crucial organisms are lost progressively as populations undergo the second epidemiological transition (modern urban environment). Recently evolved sporadic 'childhood infections' are not likely to have evolved immunoregulatory roles, and epidemiology supports this contention. The consequences of the loss of the Old Friends and distortion of the microbiota are aggravated by other modern environmental changes that also lead to enhanced inflammatory responses (obesity, vitamin D deficiency, pollution (dioxins), etc.). The range of chronic inflammatory disorders affected may be larger than had been assumed (allergies, autoimmunity, inflammatory bowel disease, but also coeliac disease, food allergy, vascular disease, some cancers, and depression/anxiety when accompanied by raised inflammatory cytokines).Keywords
This publication has 56 references indexed in Scilit:
- Macroparasites, innate immunity and immunoregulation: developing natural modelsTrends in Parasitology, 2010
- Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrusInflammatory Bowel Diseases, 2010
- Viruses in the faecal microbiota of monozygotic twins and their mothersNature, 2010
- Healthy young women with serotonin transporter SS polymorphism show a pro-inflammatory bias under resting and stress conditionsBrain, Behavior, and Immunity, 2010
- Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43Nature, 2009
- Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioningMucosal Immunology, 2009
- The gut microbiota shapes intestinal immune responses during health and diseaseNature Reviews Immunology, 2009
- Differential NF-κB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune toleranceProceedings of the National Academy of Sciences of the United States of America, 2009
- A core gut microbiome in obese and lean twinsNature, 2008
- Specific Microbiota Direct the Differentiation of IL-17-Producing T-Helper Cells in the Mucosa of the Small IntestineCell Host & Microbe, 2008