In a recent study, published in Clinical & Experimental Allergy by Heidi Kääriö et al., using samples from the Protection Against Allergy-Study in Rural Environments (PASTURE) birth cohort, demonstrate that farm exposures (stables, hay barn, farm milk) at age 4.5 years is linked to amplified Th1-type cytokine production.
There have been recent advances into the understanding of how farming exposures might differentially affect various asthmatic phenotypes. Based upon age and type of farming exposures, a wide range of studies have demonstrated protective or deleterious effects of the farming environment on asthma conditions.
The evidence supporting the theory of farming exposures as variably protective against the development of asthma and in support of the “hygiene hypothesis” is strongest in several European pediatric cohorts.
The hygiene hypothesis, or the “Old Friends” hypothesis, suggests that one reason for the increasing incidence of chronic inflammatory disorders such as allergies, inflammatory bowel disease (IBD) and autoimmunity (e.g. Type 1 diabetes; multiple sclerosis) in developed countries since the mid-19th Century is the depletion from the urban environment of immunoregulation-inducing organisms that accompanied mammalian evolution.
In specific countries such as the United Kingdom and Australia, the prevalence of asthma and atopic skin reactivity has increased, while in other countries such as Hong Kong, Germany, and Italy there has been an increase in atopy, but not asthma. Further, numerous studies report an inverse correlation for atopy for children who were raised on a farm versus nonfarm children, suggesting that farming is protective of atopy.
The Allergy and Endotoxin Study (ALEX) conducted from 1999–2004 and the Prevention of Allergy Risk factors for Sensitization in children related to Farming and Anthroposophic Lifestyle (PARSIFAL) project conducted from 2001–2004 have been important studies demonstrating farming exposures as protective against atopic and asthmatic conditions.
The more recent GABRIELA studies demonstrate similar findings in relation to asthma and allergy as the ALEX and PARSIFAL studies. The GABRIELA study was a large European study, including 8,334 school children in Germany, Switzerland, and Austria, and demonstrated decreased prevalence of asthma and atopy in children exposed to farming environments compared to children not exposed to farming environments.
One of the GABRIELA studies looked at the settled dust from children’s rooms and evaluated it for culture of bacterial and fungal organisms. Gram negative bacterial rods in the study homes were noted to confer protection against atopy. This finding reinforces the theory of endotoxin burden protecting against the development of atopy in children.
Potential explanations for the immune-protective effects of these various farming exposures have focused on innate immune signaling pathways, particularly the highly conserved Toll-like receptor (TLR) recognition signaling pathways. In general, activation of TLRs enhance T-helper (Th)1 immune responses as opposed to the allergic, Th2 polarized immune responses. Including the theory that early farm exposure (including in utero) modulate the innate immune system.
In their study, published in Clinical & Experimental Allergy, Heidi Kääriö et al., the research group from Finland and Germany report that peripheral blood mononuclear cells (PBMCs) from farm children produced more Th1-associated cytokines such as IL-12 and interferon (IFN)-γ, and immunoregulatory cytokines such as IL-10. Interestingly, the number of farm exposures correlated with higher IFN-γ levels.
Children growing up on a farm have significantly less asthma, hay fever and atopic reactions. Farm exposure provides protection from childhood asthma and allergic diseases, but the causal mechanisms remain poorly understood.
It is also known that T helper (Th) 2-type cytokines such as interleukin (IL)-4, IL-5 and IL-13 drive allergic/asthma reactions, whereas Th1-type cytokines antagonize these effects.
Thus, growing up on a farm, in early childhood, and its related Th1-type immune responses may be linked to suppressed, allergy related Th2-type responses, and this may provide help explaining the protection of farming lifestyle on asthma and allergy development in children.
Source: Clin Exp Allergy, 2015 Sep 12. doi: 10.1111/cea.12636. [Epub ahead of print]
Updates
2021
As per a recent 2021 opinion article by Erika von Mutius, a German pediatrician and allergologist, the protective effect of a traditional farm exposure on the development of childhood asthma and allergies as documented in numerous studies is very robust. According to this article there are two main pillars of the protective farm effect – the exposure to animal sheds, in particular cowsheds, and the consumption of unprocessed cow’s milk.
Keping in mind that cowsheds and unprocessed cow’s milk are “soups” containing myriads of potentially relevant elements. Moreover, the diversity of farm animal exposure during pregnancy has been associated with lower risk of atopic dermatitis and higher IFN-y and TNF-α levels in supernatants of cord blood mononuclear cells stimulated with LPS.
Finally, the diversity of the environmental and human nasal microbiome, respectively, have been associated with lower risk of asthma in the farm populations.
2022
A 2022 review discussed why living on a farm was shown to be protective on the development of asthma and allergic diseases. According to the authors several studies indicating that children from rural farming environments were found to have a risk reduction of 32%–78% for developing asthma compared with children from nonfarming rural surroundings.
The authors summarized the major factors contributing to the farm-protective effects including:
- The presence of livestock in proximity of the farming family and exposure to silage and hay.
- The bacterial cell wall component LPS or endotoxin present in high concentration in the farm environment of the children.
- The role of breastfeeding, food diversity, the gut microbiome and farm-milk.
The authors concluded that living on a farm, including nutrition influence the immune homeostasis either by regulating the innate immune system or by induction of regulatory T cells or Th1-type immune responses. Of note, they stated that one crucial “window of opportunity” for the beneficial effect of these exposures seems to be either intrauterine or early in childhood.
Furthermore, the authors mentioned that diversity plays an important role on the protective effect of farm environment on asthma and allergic diseases, (a) as the diversity of environmental microbes, (b) as the diversity of the gut microbiome, and (c) as the diversity of the nutrition.
2023
A 2023 review summarized the current knowledge on environmental factors such as microbiome or geographical locations with harmful or protective effects for human health. And, the latest findings on the interaction of environmental factors with innate and adaptive regulation of the immune system. According to the authors, multiple environmental factors, classified either as protective or harmful, interact with and thus modulate the innate as well as the adaptive part of the human immune system and its functionality via different routes of exposure.
Of note, the authors believe that early life represents a critical window of opportunity but also vulnerability influencing the subsequent development of a child’s immune system. Furthermore, pre- as well as postnatal environmental exposures shape the still developing immune system by regulation of innate and adaptive cellular differentiation, (un)balancing T cell responses, as well as modulation of cytokine secretion.
2024
A 2024 study mimicking the in vivo environmental exposure identified a novel profile of immune-regulatory markers using mass cytometry demonstrating decreased asthma-associated markers following farm-dust stimulation.
In brief, the authors of this study demonstrated a novel insight into cell type-specific regulation of cellular frequencies and functional marker expression in innate and adaptive immune cell populations as an important contribution explaining the farm-dust specific asthma-protective effect.
Some of the major findings of the study included the data that farm-dust stimulation induced cell type-specific regulation: the farm-dust stimulation comprised opposing regulation of immune-cell frequencies – downregulated innate cell populations (monocytes/DCs, NK-cells) and upregulated adaptive populations (B-cells, CD4+ T-cells), reduced CD4+ CD25− T-cell proliferation, and differential cell type-specific functional marker expression. According to the authors, their findings may be key for further studies on asthma prevention in childhood.
2025
A 2025 review summarized the environmental determinants of immune tolerance in asthma and allergy, and outlined future research directions toward precision prevention. Of note, according to the authors the early-life exposures are particularly critical.
Conforming to the authors, major factors such as pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development.
The authors also provided the major highlights and conclusions from their summary that include:
- The global rise in allergy underscores the role of the exposome in immune tolerance.
- Early-life exposures critically shape long-term immune programming and allergy risk.
- The barrier–microbiota–immune axis links environment to tolerance or allergy.
- Translational strategies include biodiversity, nutrition, and microbiome-based therapies.
- Future directions emphasize exposome measurement, causality, and systems immunology.
The authors concluded that major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology.
Cover image credit (right panel): The Hygiene Hypothesis in which it is argued that factors that promote predominance of a Th2 versus Th1 cytokine response leads to the allergic asthma phenotype. From Busse WW, Lemanske RF Jr.: Asthma, NEJM Feb 1;344(5):350-362, 2001. From: Thoracic Key; Diagnosis and Management of Asthma https://thoracickey.com/diagnosis-and-management-of-asthma/
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