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- new Recent Lectures page. New items on Interviews page
- new paper in Psychiatry page
- new book chapters in Books page
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This site provides rapid access to our thinking on the "Old Friends Hypothesis", a reformulation of the hygiene hypothesis as a crucial branch of "Darwinian" or "Evolutionary" medicine.

The bottom line is that in order to function correctly the immune system needs "data" from biodiverse microbial inputs. These inputs are absolutely crucial in early life, but continue to be important in adulthood and old age. Without appropriate microbial inputs the regulation of the immune system is faulty, and the risk of chronic inflammatory disorders increases. These increases are already striking in high income settings, and are increasing globally as prosperity increases. This happens because there are life-style changes, described in these pages, that diminish the microbial inputs, and distort the microbiota/microbiome.

The pages that follow contain mostly recent publications (and some from other authors), together with their abstracts, and links that will enable most of them to be downloaded.... when that is not possible, email me and I will send a copy if I can.

We discuss the evolutionary theory and immunological mechanisms behind the Old Friends Hypothesis, and point out the implications for human health and wellbeing.

A particular interest, that has been explored with colleagues in Germany and the USA, is the reduced stress resilience and the increased prevalence of depression in modern city-dwellers. We argue that this is at least partly secondary to defective regulation of the immune system attributable to the "Old Friends" mechanism.

Click below to see brief descriptions of the other pages

  • Old Friends
    The pages first describe the "Old Friends" hypothesis, and why this Darwinian concept usefully expands and corrects the original hygiene hypothesis, and increases its explanatory power in several clinical domains. The links between microbial exposures and socioeconomic status are also considered.

    The bottom line is that the immune system needs "data" in early life in order to function correctly. Without appropriate microbial inputs the regulation of the immune system is faulty, and the risk of chronic inflammatory disorders increases.

    It is becoming clear that the modern deficit in microbial exposures is not primarily a consequence of hygiene in the home, which remains essential to human health. The causes of the reduced exposures are antibiotics, lifestyle changes that limit transmission of maternal microbiota to the infant, or that limit exposure to the microbiota of the natural environment, and unvaried diets. Interestingly, evidence for the role of the natural environment is increasing particularly fast.
  • Psychiatry Enter description here.
    This page deals with the implications of faulty immunoregulation for psychiatry, and in particular for depression and reduced stress resilience. If regulation of the immune system is impaired, then a given level of stress will cause abnormally high and persistent levels of systemic inflammation. This persistent inflammation drives malfunctions in the central nervous system that are manifested as certain forms of depression. There is now mounting evidence that such forms of depression can be ameliorated by anti-inflammatory treatments.
  • Green Space Enter description here.
    Exposure to green spaces improves physical and psychological health. The Old Friends hypothesis provides a mechanism that can be documented by physiological measures that relate directly to the disorders from which green spaces protect us.

    We do not doubt that there is a psychological component, analogous to "habitat selection" in other species, that drives wellbeing and relaxation when we are exposed to green spaces. But just as important, and now readily proven, our immune systems have evolved to require inputs from the microbial biodiversity of the natural environment. This issue is also considered in the microbial biodiversity page.
  • Microbial biodiversity
    Exposure to microbial biodiversity, especially in the perinatal period (pregnancy and early life) is essential for the developmental and epigenetic establishment of the immune system, endocrine system and metabolism. There appears to be a "window of opportunity" in early life when crucial adjustments are made to these systems, that have life-long effects.

    Microbial biodiversity provides data in the form of molecular signals (for example, in the airways), molecular structures (for repertoire development), and organisms for the symbiotic microbiota.

    Although the perinatal period is the most critical, it is clear that we also need microbial biodiversity in the gut microbiota in adulthood, and a decline in biodiversity in old age correlates with increasing levels of inflammation, and declining health.
  • Interviews
    Radio or television interviews on the topic of the "Old Friends Hypothesis" and its clinical implications. Where available the interviews can be played in the page, or accessed via a link provided.
  • Recent Lectures
    Details of recent lectures that seem particularly significant. Links are given to PDF files of the powerpoint presentation, or to videos, when available.
  • Book
    Information about books to which I have recently contributed chapters.

    Also information about a book on the topic of this website that I edited and partly wrote. This
    book uses the Old Friends hypothesis as background to a discussion of the increasing prevalences in high-income settings of chronic inflammatory disorders (allergies, autoimmunity, inflammatory bowel disease) and of disorders linked to persistent redundant inflammation (cardiovascular disease, metabolic syndrome, depression, some cancers).

    These increases are attributable to a broad defect in immunoregulation in high-income settings, which is at least partly driven by failing microbial inputs to the immune system.

    The authors discuss the potential role of failing immunoregulation in the aetiology of chronic inflammatory diseases of the organ systems that are the fields of their specialist expertise.

    The book was published in 2009, so parts of it are somewhat dated.
A link to those of my publications that are listed in PUBMED. Many of them can be downloaded free of charge by anyone.

This link goes to the UCL site

Prof Graham A.W. Rook, BA, MB, BChir, MD.
Centre for Clinical Microbiology
UCL (University College London)                email:-