The hygiene hypothesis survives as biology and fails as an argument about cleanliness

The core biological claim behind the hygiene hypothesis has held up: children exposed to a wider range of environmental microbes in early life are less likely to develop asthma and allergy, and the effect has been traced to specific exposures and specific immune mechanisms [s2] [s3]. The popular version of the claim — that modern cleanliness caused the rise in allergic disease — has not. A Delphi consensus of infectious and allergic disease experts concluded there is no good evidence that hygiene, as the public understands the word, is responsible for the changes in microbial exposure that matter, and argued the term itself should be abandoned as a misleading misnomer [s4].

The idea takes its name from a short paper published in the BMJ on 18 November 1989 under the title "Hay fever, hygiene, and household size" [s1]. Almost everything now known about the mechanism came later, and much of it came from farms.

What the farm studies found

Two cross-sectional European studies compared children living on farms with a reference group, measuring both disease and the diversity of microbial exposure [s2]. In PARSIFAL, mattress dust was screened for bacterial DNA using single-strand conformation polymorphism analysis, a method that detects environmental bacteria which cannot be cultured; in GABRIELA, settled dust from children's rooms was assessed for bacterial and fungal taxa by culture [s2].

In both studies, farm children had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms [s2]. Diversity of exposure was inversely related to asthma risk: odds ratio 0.62 (95% CI 0.44-0.89) in PARSIFAL and 0.86 (0.75-0.99) in GABRIELA [s2]. Specific exposures carried their own associations — species in the fungal taxon eurotium (adjusted odds ratio 0.37, 0.18-0.76) and a set of bacterial species including Listeria monocytogenes, Bacillus and Corynebacterium (0.57, 0.38-0.86) [s2].

The conclusion the authors drew is narrower than the popular one: the wider range of microbes explains a substantial fraction of the inverse relation between asthma and growing up on a farm [s2]. Not all of it, and not asthma in general.

The natural experiment that isolated the variable

The strongest version of this evidence comes from two US agricultural communities whose lifestyles are similar in most respects but whose farming practices are not. The Amish farm traditionally; the Hutterites use industrialised methods [s3].

Researchers studied 60 Amish and Hutterite children, measuring allergens and endotoxins in house dust, characterising the indoor dust microbiome, and profiling immune cells and gene expression from whole blood [s3]. Despite similar genetic ancestries and lifestyles, the prevalence of asthma was 4 times as low in the Amish and allergic sensitisation 6 times as low, while median endotoxin levels in Amish house dust were 6.8 times as high [s3]. The proportions, phenotypes and functions of innate immune cells differed profoundly between the two groups [s3].

Then the study did the thing observational comparisons usually cannot. Dust extracts from Amish and Hutterite homes were instilled intranasally into mice in a model of experimental allergic asthma [s3]. Amish dust significantly inhibited airway hyperreactivity and eosinophilia; Hutterite dust did not [s3]. And the protection disappeared in mice deficient in MyD88 and Trif, two molecules central to innate immune signalling [s3].

That last step is what raises this above correlation. It identifies a candidate pathway, and shows the effect vanishes when the pathway is disabled. It is still a mouse model, and the human arm is 60 children in two communities [s3].

Why the name is the problem

The Delphi exercise that recommended abandoning the term surveyed six experts in infectious and allergic disease to elicit a consensus view [s4]. It accepted the underlying biology: interaction with microbes inhabiting the natural environment and the human microbiome plays an essential role in immune regulation, and changes in lifestyle, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, contributing to failure of immunotolerance and increased risk of allergic disease [s4].

What it rejected is the causal story attached to the name. There is no good evidence that hygiene, as the public understands it, is responsible for the clinically relevant changes to microbial exposure [s4]. The distinction is between washing your hands and where you live, what you eat, how you were born, and what antibiotics you took — and only the first of those is what people hear in the word "hygiene".

The report's practical framing is targeted hygiene: a risk-assessment approach that maximises protection against pathogen exposure while allowing essential microbes to spread between family members [s4]. Its list of candidate strategies — natural childbirth, breastfeeding, more social exposure through sport and outdoor activity, less time indoors, diet, appropriate antibiotic use — is offered as things that may help, with the emphasis on early life [s4]. A Delphi consensus is expert opinion, formally elicited, not a trial; none of those strategies has been shown in a randomised comparison to prevent allergic disease.

What remains unresolved

Nobody has shown which exposure, at which age, in which dose, does the protective work. The farm studies point at diversity and at particular taxa [s2]; the Amish comparison points at endotoxin and innate immune signalling [s3]. Neither identifies a reproducible intervention, and there is no trial in which raising a child's microbial exposure prevented asthma.

The public health consequence of the misnaming is the reason specialists keep pressing on it. A hypothesis that is heard as "children are too clean" invites people to be less careful about infection, which is a straightforward harm, in exchange for a benefit that has never been demonstrated to follow from being less clean [s4].

Sources

• Hay fever, hygiene, and household size — BMJ, 1989-11-18
• Exposure to environmental microorganisms and childhood asthma — New England Journal of Medicine, 2011-02-23
• Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children — New England Journal of Medicine, 2016-08-03
• Time to abandon the hygiene hypothesis — Perspectives in Public Health, 2016-06-27