Microbial exposures that establish immunoregulation are compatible with targeted hygiene
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.
Download it here
Is the term “Hygiene hypothesis” now obsolete?
Much discussion of the “Hygiene Hypothesis” is misleading, even dangerous, because it fails to approach the issue from an evolutionary point of view. (More about this in a recent interview)
The microorganisms that we need to encounter are those with which we co-evolved. In the past we lived in the natural environment, and until recently our homes were built with natural products (timber, mud, dung, thatch) so the microbiota of our homes resembled that of the natural environment. A modern home, built with biocide-treated timber, plasterboard and plastic is entirely different and it devlops a different microbiota. Moreover, when modern homes become damp and degraded, the microbiota can include organisms that produce secondary metabolites that are harmful to humans because we didn’t encounter them in our evolutionary past. So we gain nothing from encountering the microbiota of the modern urban home, which should obviously be kept clean.
On the other hand, most recent epidemiology indicates that exposure to the microbiota of the home can be beneficial if it resembles that of the natural environment…… just as an evolutionary approach would predict. Cats, dogs, gardens, a rural environment or living on a farm all bring the natural environment into the home. So the bottom line is, keep your home clean, but adjust your lifestyle to maximise your exposure to the natural environment!
In summary, home hygiene is not an important factor in the changes to our microbial exposures, so the misleading term "Hygiene Hypothesis" should be replaced by "Old Friends Hypothesis" or the "Biodiversity Hypothesis"
The background to the OLD FRIENDS HYPOTHESISThe human ecosystem
We are not individuals. We are ecosystems with microbial partners (microbiota) that are involved in the development (particularly in early life) and function of essentially every organ, including the brain. In fact we have more microbes in our guts than we have human cells in our bodies, and vastly more microbial DNA and genes than human genes.
This situation appeared with the evolution of vertebrates about 500 million years ago, and gives vertebrates enormous adaptability and flexibility because microbial genes can evolve rapidly when we change environment, diet or lifestyle. At the same time vertebrates evolved a more complex immune system that is able to achieve the tricky task of tolerating and “farming” our many hundreds of species of microbial partners (microbiota), while simultaneously protecting us from pathogens.
Failing regulation of our immune systems
However the high-income countries are now experiencing diseases where the immune system is attacking targets that it should not attack, such as our own tissues (multiple sclerosis, Type 1 diabetes), or harmless molecules in the air we breathe (hay fever, allergic asthma), or gut contents (inflammatory bowel diseases).
Our immune systems are also failing to terminate episodes of inflammation that are no longer needed, and persistent inflammation, even if accompanied by no apparent symptoms, predisposes to cardiovascular disease, obesity and depression and some cancers.
So why are our immune systems attacking things they should not attack?
At least part of the answer lies in changes to the composition of the gut microbiota and loss of its biodiversity. This is easily proved by transferring gut microbiota from obese or depressed humans into the guts of animals, which then develop similar symptoms.
Why are these changes occurring?
Lifestyle changes, antibiotics, caesarean births and lack of breast-feeding limit the transmission of maternal microbiota to the next generation. Then, unvarying diets lacking plant-derived fibre and polyphenols aggravate this loss of biodiversity. We also have less contact with the natural environment which is the source of many of the microbial partners that we need.
Without these microbial inputs in early life our immune systems, endocrine systems and metabolic systems do not develop correctly, and can malfunction.
So domestic hygiene is not an important cause of the poor regulation of our immune systems that we see in high-income settings. Other lifestyle changes described in these pages are to blame.
Click here to download a paper reviewing this topic.
Below we list papers on this topic, and on the implications for autoimmunity, and for the increase in cancers associated with inflammation.
The evolution of the immune systemTo understand why we evolved the need for contact with microbial biodiversity from the Natural Environment it is important to understand the evolution of the immune system, as mentioned in the previous section. The chapter illustrated below describes this in some detail in the highly recommended Oxford Handbook of Evolutionary Medicine (the chapters from this book can be downloaded individually). The chapter also describes some of the pathways and molecular mechanisms of the health benefits of exposure to microbial biodiversity. However a much more detailed account of the mechanisms is in press (reference listed below).
Rook G. Darwinian medicine: why have we evolved to require continuing contact with the microbiota of the natural environment? In: Hurst CJ, editor. Microbes: The Foundation Stone of the Biosphere: Springer Nature Switzerland AG, Gewerbestrasse 11, 6330 Cham, Switzerland; 2020
LANCET paper on evolution and microbiota.
Rook G, Bäckhed F, Levin BR, McFall-Ngai MJ, McLean AR.
"Evolution, human-microbe interactions, and life history plasticity."
Lancet. (2017), Jul 29 390(10093):521-530. doi: https://doi.org/10.1016/S0140-6736(17)30566-4
Abstract. A bacterium was once a component of the ancestor of all eukaryotic cells, and much of the human genome originated in microorganisms. Today, all vertebrates harbour large communities of microorganisms (microbiota), particularly in the gut, and at least 20% of the small molecules in human blood are products of the microbiota. Changing human lifestyles and medical practices are disturbing the content and diversity of the microbiota, while simultaneously reducing our exposures to the so-called old infections and to organisms from the natural environment with which human beings co-evolved. Meanwhile, population growth is increasing the exposure of human beings to novel pathogens, particularly the crowd infections that were not part of our evolutionary history. Thus some microbes have co-evolved with human beings and play crucial roles in our physiology and metabolism, whereas others are entirely intrusive. Human metabolism is therefore a tug-of-war between managing beneficial microbes, excluding detrimental ones, and channelling as much energy as is available into other essential functions (eg, growth, maintenance, reproduction). This tug-of-war shapes the passage of each individual through life history decision nodes (eg, how fast to grow, when to mature, and how long to live).