The Changing Microbial Environment and Chronic Inflammatory Disorders
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The Changing Microbial Environment and Chronic Inflammatory Disorders Graham A.W. Rook, BA, MB, BChir, MD There is much to be gained from examining human diseases within the expanding framework of Darwinian medicine. This is particularly true of those conditions that change in frequency as populations develop from the human ‘‘environment of evolutionary adaptedness’’ to the living conditions of the rich industrialized countries. This development entails major changes in lifestyle, leading to reductions in contact with environmental microorganisms and helminths that have evolved a physiologic role as drivers of immunoregulatory circuits. It is suggested that a deficit in immunoregulation in rich countries is contributing not only to increases in the incidence of allergic disorders but also to increases in other chronic inflammatory conditions that are exacerbated by a failure to terminate inappropriate inflammatory reponses. These include autoimmunity, neuroinflammatory disorders, atherosclerosis, depression associated with raised inflammatory cytokines, and some cancers.
n 1989, Strachan showed that in young adults, a history of hay fever was inversely related to the number of children in the family when the subject was 11-years old.1 Further studies suggested that having many siblings, especially older ones, correlated with diminished risk of hay fever, and these findings were considered consistent with a protective influence of postnatal infection, which might be lost in the presence of modern hygiene.2 So the ‘‘hygiene hypothesis’’ was born. The concept was initially vague and lacked mechanistic explanations, so in the 28 years since the original study, a multitude of different, often mutually exclusive, versions of this hypothesis have been considered. Often this has led to the ‘‘disproving’’ of hypotheses that few had intended to propose in the first place. However, during the last 9 years, an essentially new hypothesis has emerged, which we have preferred to designate ‘‘the old friends hypothesis.’’ This hypothesis might not be relevant to Strachan’s original findings, which remain unexplained, but it does have very broad importance for understanding the influence of changing patterns of microbial exposure on trends in human disease and is leading to encouraging clinical trials. Moreover, the old friends hypothesis belongs within the rapidly growing
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Graham A.W. Rook: Centre for Infectious Diseases and International Health, Windeyer Institute of Medical Sciences, University College London, London, UK. Correspondence to: Graham A.W. Rook, BA, MB, BChir, MD, 46 Cleveland Street, London, UK W1T 4JF; e-mail: [email protected].
DOI 10.2310/7480.2008.00013
framework of ‘‘evolutionary medicine,’’ which seeks to clarify our understanding of disease by considering our evolutionary history. This review first outlines various ‘‘failed’’ versions of the hygiene hypothesis and then describes the old friends hypothesis and its implications not only for allergic disorders but also for other chronic inflammatory disorde
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