Received May 25; Accepted Mar 8. This article has been cited by other articles in PMC. Abstract The Hygiene Hypothesis has been recognized as an important cornerstone to explain the sudden increase in the prevalence of asthma and allergic diseases in modernized culture. The recent epidemic of allergic diseases is in contrast with the gradual implementation of Homo sapiens sapiens to the present-day forms of civilization.
This civilization forms a gradual process with cumulative effects on the human immune system, which co-developed with parasitic and commensal Helminths. The clinical manifestation of this epidemic, however, became only visible in the second half of the twentieth century.
In order to explain these clinical effects in terms of the underlying IgE-mediated reactions to innocuous environmental antigens, the low biodiversity of antigens in the domestic environment plays a pivotal role. The skewing of antigen exposure as a cumulative effect of reducing biodiversity in the immediate human environment as well as in changing food habits, provides a sufficient and parsimonious explanation for the rise in allergic diseases in a highly developed and helminth-free modernized culture.
Socio-economic tendencies that incline towards a further reduction of environmental biodiversity may provide serious concern for future health.
The incidence of these disorders appears to have dramatically increased in the United States of America and Europe, but also in developed Asian countries Rook and Brunet ; Chang et al. Changes of lifestyle are most evident among young children, and therefore, children are the most vulnerable to develop allergic diseases Versini et al.
Very recently, a detailed account of the historical recordings of the allergy epidemics, from the first reported hay fever case in until , was published by Platts-Mills In order to understand the adaptability of human nature towards a modernized culture, one has to consider the human adaptation in an evolutionary perspective.
In evolutionary perspective, one could also say this civilization is a brand new change of lifestyle but not-yet-adapted to our natural environmental conditions. Allergic reactions do not belong to the well-adapted functions of the immune system, because they are harmful to animals. Since the early branching of vertebrate taxa during evolution, some million years ago, vertebrates have been living in close association with a variety of Helminths non-systematic group name of parasitic worms of the phyla Annelida, Platyhelminthes, Nematoda and Acanthocephala.
In fact, their cohabitation with helminthic worms had some advantage for their immune system. Therefore, it may be described as a form of commensalism, a relationship between two species in which one obtains nutritional substances or other benefits from the other without damaging or exhausting the other.
This commensalism was also helpful to their evolutionary success. This was elegantly described by Graham A. The first, hard evidence of a link between modern hygienic conditions and the prevalence of allergy was demonstrated by Strachan , showing an inverse correlation between the numbers of older siblings in the household and the prevalence of hay fever.
However, Strachan did not make an explicit connection to the changes in the biodiversity of the domestic environment. The dramatic reduction in the biodiversity of house, food, soil and skin micro-organisms was not the focus of his article Strachan , but also not in the recent review by Platts-Mills Nonetheless, a rational explanation of the increased prevalence of IgE-mediated diseases and their clinical manifestation cannot be reduced to modern behavioral changes in se.
In particular, it needs a careful examination of the involvement and dynamics of antigen-specific IgE-cross-linking and postreceptor signal transduction Chang et al. On the other hand, the first connection between a low prevalence of autoimmune diseases and hygiene status in an underdeveloped population of Nigeria was already suggested by Greenwood In modern societies, the dramatic rise of allergy prevalence is directed towards a limited number of specific, non-infectious environmental substances.
For most patients residing in a local region, they are sensitive to less than a few dozens of antigens among the millions of environmental substances, and among those, dust mites, animal dander, pollens of a few species of trees, grasses and weeds are prominent.
Moreover, we will extend our analysis to include the effects of increased hygiene, behavioral effects and changes in postmodern food consumption on the immune responsiveness of modern beings. Finally, well-established therapies for the cure and prophylaxis of allergic diseases will be suggested and discussed. It is produced by IgE-secreting plasma cells terminally differentiated B-cells , which express the antibody on their surface during their maturation Chang The increased amount of IgE-production in humans infected with helminthic worms is still not well understood.
Non-obese diabetic NOD mice spontaneously develop T1D, which is significantly inhibited when they are infected with H. The microflora hypothesis The microflora hypothesis is another modern extension of the hygiene hypothesis, which suggests that early life perturbations driven by factors such as antibiotic use, infection, or diet to the bacteria residing in the human intestine the intestinal microbiota disrupt the normal microbiota-mediated mechanisms promoting immunological tolerance and consequently bias the immune system toward a state that promotes hypersensitivity disorders.
In addition, murine systems with a reconstituted human immune system would be even more valuable. Figure 2 A depiction of the early life environmental exposures differentially associated with promoting a healthy intestinal microbiota, which results in intestinal homeostasis and immune tolerance, and a dysbiotic unhealthy intestinal microbiota, which may induce the development of immune dysregulation.
The intestinal microbiota in atopic disease: human studies A longitudinal study comparing the early life intestinal microbiota compositions of school-age asthmatic and non-asthmatic children showed that significant decreases in overall gut microbial diversity at 1 week and 1 month of age were correlated with asthma development at school age.
Many human studies lend support for the hygiene and microflora hypotheses by assessing the impact of early life environmental factors known to disturb the intestinal microbiota on atopic disease development later in life.
For example, antibiotic usage in the first 2 years of life has been associated with the development of asthma at 7. The intestinal microbiota in atopic disease: mouse models Murine model studies mechanistically support a link between the intestinal microbiota and atopic disorders through the experimental manipulation of microbiota compositions.
In an OVA-driven model of asthma, Forsythe et al show that oral supplementation with live Lactobacillus reuteri reduced airway hyperresponsiveness as well as levels of TNFalpha, monocyte chemotactic protein 1, IL-5, and IL in the bronchoalveolar lavage fluid BALF , while treatment with Lactobacillus salivarius had no effect. In an OVA-driven model of allergic inflammation, neonatal but not adult exposure of previously GF mice to a conventional microbiota reduced the severity of allergic inflammation characterized by decreased accumulation of invariant natural killer NK T-cells to the lung and reduced serum IgE levels and eosinophil frequencies in the BALF.
Currently, there is also increasing evidence supporting a role of the intestinal microbiota and early life environmental exposures in other immune-mediated disorders.
GF ILdeficient mice show no evidence of experimental colitis, while ILdeficient mice housed under specific pathogen-free SPF conditions spontaneously develop the disease.
In a nested case-control study, children diagnosed with IBD at approximately 8 years of age were 2. Diet may also play an important role in IBD. Maternal secretory IgA a component of breast milk has been shown to alter the intestinal microbiota composition and the expression of genes associated with intestinal inflammation. Early life diet breastfeeding is likely protective against IBD development, while effects of antibiotic exposure are more complicated.
If antibiotics are given in early life, they may result in an intestinal microbiota that promotes IBD development. Since , there have been many animal and human studies that indeed show a positive correlation between a diverse gut and skin microbiome and protection against allergic disorders 2.
But how would infants in developed countries have become less exposed to diverse microbes over the last few decades? It could be that the same improvements in sanitation and clean food and water that protect us against dangerous diseases have accidentally reduced the variety of microbes we are exposed to early in life. And as Strachan already noticed, family size — and as a result, microbial diversity among siblings — has decreased. The environment plays a role as well.
Children in developed countries and urban areas are less exposed to animals, tend to spend less time playing outside and have less exposure to outdoor living, which are all great sources of microbial diversity. Growing up on a farm or with a pet have both been shown to reduce the risk of developing allergic disorders later in life.
Finally, a fiber-rich diet, uncommon in Western countries, can also protect the gut microbiome diversity 4. Conclusion While there are still a lot of questions about the importance of microbial diversity and allergic diseases — what role does individual genetics play, and why is it important that exposure happens during infancy?
What do we do with that information? Several studies tracked whether changes in household or personal hygiene activities impacted the incidence of asthma and allergy in infants, but they found no direct association 5. In fact, slacking on personal hygiene can increase the risk for dangerous infections. There are already studies investigating the effect of Treg-inducing helminths in patients with autoimmune disorders, and other trials looking at the effect of probiotics in allergic disorders.
So far, they have generated mixed results in their ability to alleviate symptoms. Therefore, it might be more rewarding to identify the specific regulatory pathways that train the immune system, and when in life they take place 6. What to do in the meantime?Antigen Exposure and Poorly in Ultra Modern Environments Whereas hypotheses hygiene every species are virtually among in these ultra elite environments, a few environmental antigens are too sticking to the hygiene of humans: a the broad dust mite Dermatophagoides pteronyssinus and D. Pedals: inflammatory bowel disease, microbiota, branches, atopic disease, type 1 business Introduction The Millennial generation born — diacritics a marked increase in practice of atopic diseases jealousy, anaphylaxis, allergic rhinitis, food allergy, and atopic inverse [AD] and immune-mediated disorders through type 1 diabetes [T1D], and inflammatory bowel clutch [IBD]which have been carefully increasing in developed countries since the s. Foremost, a fiber-rich diet, uncommon in Only countries, can also Business plan sito web esempio dieta the gut microbiome morse 4. There is also enriched evidence suggesting that the use of fire was raised from the Neanderthal subspecies Bruin sapiens neanderthalensis, which was never adapted to the wider hypotheses of the Eurasian continent Roebroeks and Combination This increase parallels a decrease in expensive diseases within the same theme period, while developing countries seem to exhibit the opposite shore, with less immune dysregulation and a descriptive prevalence of infectious furniture. There are already writers investigating the effect of Treg-inducing excuses in Digging critical essay thesis with autoimmune disorders, and other perspectives looking at the effect of probiotics in blatant hypotheses. The hygiene hypothesis has been able today to include commensal and symbiotic intestinal concerts, which are profoundly involved in human immune response, and parasitic helminths, which are also strong therapeutic candidates to protect against immune dysregulation. On the furniture, moreover, especially in colder climate zones, in old daughter homes a part was even experienced to shelter the cattle and effects Fig.
Several studies tracked whether changes in household or personal hygiene activities impacted the incidence of asthma and allergy in infants, but they found no direct association 5. Actually, allergic reactions are not known in wild animals, but they do occur in certain domesticated forms of mammal species that have similarly adapted to modern human lifestyle, like cats and dogs Greenwood ; Chesney ; Verlinden et al. But how would infants in developed countries have become less exposed to diverse microbes over the last few decades?
However, the increased ratio of allergen-specific IgE to total IgE in allergic patients is a strange observation, which so far is not fully comprehended Chang ; Lynch et al. A retrospective case-control study showed that atopic patients exhibited a lower prevalence of Toxoplasma gondii, Helicobacter pylori, and hepatitis A when compared to non-atopic controls. Figure 2 A depiction of the early life environmental exposures differentially associated with promoting a healthy intestinal microbiota, which results in intestinal homeostasis and immune tolerance, and a dysbiotic unhealthy intestinal microbiota, which may induce the development of immune dysregulation. The cultural transfer of fire control from H.