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Resolution of the "Hygiene Hypothesis" paradox?

A new paper in the Journal of Allergy and Clinical Immunology (JACI) discusses the conflict between the need for hygiene and cleaning to protect us from pathogens, and the equally essential need for microbial exposures. This paper uses new information to suggest a framework for resolving the conundrum.

TITLE:- Microbial exposures that establish immunoregulation are compatible with targeted hygiene

Download it here
Topics discussed include the non-specific health benefits of vaccines, the Th2-adjuvanticity of some cleaning agents, and the association of low socio-economic status (SES) with distorted microbial inputs. We (Graham Rook and Sally Bloomfield) also discuss "Targeted Hygiene" and how to implement it.

A recent paper (Roslund et al, 2020) shows that exposing children to biodiversity from the natural environment increases biomarkers of immunoregulatory mechanisms in their peripheral blood.

The playgrounds of daycare centres were modified with forest floor, sod, planters for growing annuals, and peat blocks for climbing and digging. This intervention diversified both the environmental and skin Gammaproteobacterial communities, compared to control playgrounds. These changed microbiomes were associated with increases in plasma TGF-beta1 levels and in the proportion of regulatory T cells.

COVID-19 and SARS-Cov-2
Possible roles of diminishing environmental biodiversity

Biodiversity & SARS-CoV-2 

We need to maintain the biodiversity of the natural environment

Biodiverse ecosystems are more stable because the presence of multiple species in complex networks enhances the likelihood of successful adaptation to change. But human activities are reducing biodiversity and destabilising ecosystems so that pathogens are forced to seek new hosts (see the Tab on plague for an ancient example). Meanwhile intensive high density animal farming, and animal markets that juxtapose incongruous species, provide havens for these pathogens, and increase the probability that they will enter our environment, evolve and adapt to humans.

The gut microbiota modulates the immune response to viruses in the lungs.

This has been proven in many experimental models. We must therefore ask ourselves whether the high susceptibility to COVID-19 (the infection caused by SARS-CoV-2) of black, asian and other ethnic minorities (BAME) living in Europe or the USA is partly due to racism and deprivation in these countries leading to inappropriate gut microbiota. Poverty, poor diet, poor housing and limited opportunities for spending time in green space result in suboptimal exposures to the microbiota of the natural environment, suboptimal gut microbiota and suboptimal regulation of the immune system. These effects would be exacerbated by stress, lack of exercise and lower vitamin D levels in those with pigmented skin. This possibility should be researched

Ecosystem instability and the plague

Plague is caused by the bacterium, Yersinia pestis. This bacterium was responsible for the "Black Death" (1347–1353) and also for repeated outbreaks of plague in Europe until the early 19th Century. An outbreak in England in 1665 is particularly well-documented. Recent work suggests that plague was reintroduced into Europe at intervals by the fleas of gerbils! Gerbils (Rhombomys opimus) are rodents that live in the mountains of western Central Asia in areas such as Kazakhstan. Gerbils become very numerous when there are warm springs followed by wet summers. The problem is that their fleas increase in parallel. But when the weather pattern reverts, so that warm springs followed by wet summers become rare, the rodent population collapses. Then the fleas become too numerous for the available stock of gerbils, so they are obliged to seek other hosts. Tree ring studies have revealed when such climate cycles occurred, and it has even been possible to calculate the speed at which the gerbil's fleas spread from the mountains of western Central Asia to the coast of the Black Sea, where they infected rats and humans, and got transported on ships to European ports….carrying Yersinia pestis.
Obviously the climate cycles that pushed the gerbils’ fleas to Europe were not man-made. They were natural variations. But now we face man-made climate change, coupled with pollution and monoculture, so increasingly unstable ecosystems will drive novel pathogens into human environments. SARS-CoV-2 is an example, as are SARS, MERS, Zika and Ebola. There will be more. We can be absolutely sure of that. We must hope that the COVID-19 outbreak has taught governments that in the modern world every country should be prepared for the next pandemic.

A neglected consequence of confinement

Numerous epidemiological studies in humans and experiments in laboratory models have shown that there is a crucial "window of opportunity" in early life, during which the infant must receive appropriate microbial inputs (See discussion and references on other pages of this website). These inputs provide data and signals that are needed to expand the developing immune system, and to set up correctly the control mechanisms that stop inappropriate immune responses. A failure of these inputs predisposes the child to chronic inflammatory disorders such as allergies, autoimmunity and inflammatory bowel diseases because the immune system is not "policed" correctly. Moreover many parameters of the metabolic system are also set up during this early life period. Again, the microbial inputs provide metabolic flexibility and signals that have long-term consequences. A failure of these inputs in early life can predispose to later obesity and diabetes. (Excessive use of antibiotics in early life alters and diminishes the microbiota, and therefore has a similar effect). The problem is that during confinement for COVID-19, children from wealthy homes may have gardens to play in, and this will maintain microbial inputs from the natural environment. On the other hand, children from low Socioeconomic Status (SES) backgrounds may be isolated in a small apartment in a tower block during this crucial phase of microbial input. Will we see an increase in chronic inflammatory and metabolic disorders in these low SES children as they grow older? Are we burdening these already deprived individuals with further problems in the future? Unfortunately we don't seem to have any alternative. Confinement is clearly essential.
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Plants, animals and humans, are colonized by microorganisms (microbiota) and transiently exposed to countless others. The microbiota affects the development and function of essentially all organ systems, and contributes to adaptation and evolution, while protecting against pathogenic microorganisms and toxins. Genetics and lifestyle factors, including diet, antibiotics and other drugs, and exposure to the natural environment, affect the composition of the microbiota, which influences host health through modulation of interrelated physiological systems. These include immune system development and regulation, metabolic and endocrine pathways, brain function and epigenetic modification of the genome. Importantly, parental microbiotas have transgenerational impacts on the health of progeny.
Humans, animals and plants share similar relationships with microbes. Research paradigms from humans and other mammals, amphibians, insects, planktonic crustaceans and plants demonstrate the influence of environmental microbial ecosystems on the microbiota and health of organisms, and indicate links between environmental and internal microbial diversity and good health. Therefore, overlapping compositions, and interconnected roles of microbes in human, animal and plant health should be considered within the broader context of terrestrial and aquatic microbial ecosystems that are challenged by the human lifestyle and by agricultural and industrial activities.
Here, we propose research priorities and organizational, educational and administrative measures that will help to identify safe microbe-associated health-promoting modalities and practices. In the spirit of an expanding version of “One health” that includes environmental health and its relation to human cultures and habits (EcoHealth), we urge that the lifestyle-microbiota-human health nexus be taken into account in societal decision making.

   Work with the Convention on Biological Diversity

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Diminishing global biodiversity is a major concern. Loss of diversity at the microbial level is of immediate importance to human health. Symbiotic microbiota and environmental microorganisms and their genes play crucial roles in human physiology that we are only just beginning to explore. This website concentrates on the “education” of the immune system, but we know that microorganisms also play significant roles in the development of most organ systems (including the brain), and in metabolism and regulation of energy balance. Moreover a large percentage (20-30% ??) of small molecules in peripheral blood are of microbial origin, and we have barely begun to understand the multiple roles that these molecules play. If we lose microbial biodiversity we will almost certainly encounter new health problems of which we currently have no understanding.
The Convention on Biological Diversity (CBD) has produced a remarkable review of biodiversity and human health, as described below. I have contributed to the chapter on microorganisms
The Convention on Biological Diversity together with the United Nations Environment Programme (UNEP) and the World Health Organisation (WHO) has generated the document of which the cover page is seen on the right. This document is 364 pages, with 16 chapters on all aspects of the importance of biodiversity to human health.

Chapter 8, starting on page 150, has the title “Environmental microbial diversity and noncommunicable diseases”.
G. Rook and R. Knight were lead authors, and there was also input from the CBD and other organisations. Chapter 8 can be downloaded here, but I would strongly advise readers to download the whole document (about 5MB) from the CBD website. It is freely available to anyone who is interested.
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