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Hygiene in the Industrial World:
An Unhealthy Obsession with Cleanliness?

(Released June 2011)

 
  by Kathryn Mori & Carolyn Scearce  

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  1. Atopic dermatitis and the hygiene hypothesis revisited

    Carsten Flohr and Lindsey Yeo.

    Current problems in dermatology, Vol. 41, 2011, pp. 1-34.

    Background: We published a systematic review on atopic dermatitis (AD) and the hygiene hypothesis in 2005. Since then, the body of literature has grown significantly. Objectives: We therefore repeated our systematic review to examine the evidence from population-based studies for an association between AD risk and specific infections, childhood immunizations, the use of antibiotics and environmental exposures that lead to a change in microbial burden. Methods: Medline was searched from 1966 until June 2010 to identify relevant studies. Results: We found an additional 49 papers suitable for inclusion. There is evidence to support an inverse relationship between AD and endotoxin, early day care, farm animal and dog exposure in early life. Cat exposure in the presence of skin barrier impairment is positively associated with AD. Helminth infection at least partially protects against AD. This is not the case for viral and bacterial infections, but consumption of unpasteurized farm milk seems protective. Routine childhood vaccinations have no effect on AD risk. The positive association between viral infections and AD found in some studies appears confounded by antibiotic prescription, which has been consistently associated with an increase in AD risk. Conclusions: There is convincing evidence for an inverse relationship between helminth infections and AD but no other pathogens. The protective effect seen with early day care, endotoxin, unpasteurized farm milk and animal exposure is likely to be due to a general increase in exposure to non-pathogenic microbes. This would also explain the risk increase associated with the use of broad-spectrum antibiotics. Future studies should assess skin barrier gene mutation carriage and phenotypic skin barrier impairment, as gene-environment interactions are likely to impact on AD risk. Copyright © 041_ S. Karger AG, Basel.

  2. Can oral pathogens influence allergic disease?

    Samuel J. Arbes and Elizabeth C. Matsui.

    The Journal of allergy and clinical immunology, Vol. 127, No. 5, 2011, pp. 1119-1127.

    The hygiene hypothesis contends that fewer opportunities for infections and microbial exposures have resulted in more widespread asthma and atopic disease. Consistent with that hypothesis, decreases in infectious oral diseases over the past half century have coincided with increases in the prevalence of asthma and other allergic diseases. This observation has led some researchers to speculate that exposures to oral bacteria, including pathogens associated with periodontal diseases, such as gingivitis and periodontitis, might play a protective role in the development of asthma and allergy. Colonization of the oral cavity with bacteria, including some species of periodontal pathogens, begins shortly after birth, and the detection of serum antibodies to oral pathogens in early childhood provides evidence of an early immune response to these bacteria. Current knowledge of the immune response to oral bacteria and the immunologic pathogenesis of periodontal diseases suggests biologically plausible mechanisms by which oral pathogens could influence the risk of allergic disease. However, studies investigating the association between oral pathogen exposures and allergic disease are few in number and limited by cross-sectional or case-control design, exclusion of young children, and use of surrogate measures of oral bacterial colonization. Additional studies, particularly well-designed case-control studies among very young children and prospective birth cohort studies, are needed.Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. Denaturing gradient gel electrophoresis of neonatal intestinal microbiota in relation to the development of asthma

    Carl Vael, Liesbeth Vanheirstraeten, Kristine N. Desager and Herman Goossens.

    BMC microbiology, Vol. PMC3079593, 2011, pp. 68-68.

    ABSTRACT:The extended 'hygiene hypothesis' suggests that the initial composition of the infant gut microbiota is a key determinant in the development of atopic disease. Several studies have demonstrated that the microbiota of allergic and non-allergic infants are different even before the development of symptoms, with a critical time window during the first 6 months of life. The aim of the study was to investigate the association between early intestinal colonisation and the development of asthma in the first 3 years of life using DGGE (denaturing gradient gel electrophoresis).In a prospective birth cohort, 110 children were classified according to the API (Asthma Predictive Index). A positive index included wheezing during the first three years of life combined with eczema in the child in the first years of life or with a parental history of asthma. A fecal sample was taken at the age of 3 weeks and analysed with DGGE using universal and genus specific primers.The Asthma Predictive Index was positive in 24/110 (22%) of the children. Using universal V3 primers a band corresponding to a Clostridum coccoides XIVa species was significantly associated with a positive API. A Bacteroides fragilis subgroup band was also significantly associated with a positive API. A final DGGE model, including both bands, allowed correct classification of 73% (80/110) of the cases. Fecal colonisation at age 3 weeks with either a Bacteroides fragilis subgroup or a Clostridium coccoides subcluster XIVa species is an early indicator of possible asthma later in life. These findings need to be confirmed in a new longitudinal follow-up study.

  4. Gender and the hygiene hypothesis

    Sharyn Clough.

    Social science & medicine (1982), Vol. 72, No. 4, 2011, pp. 486-493.

    The hygiene hypothesis offers an explanation for the correlation, well-established in the industrialized nations of North and West, between increased hygiene and sanitation, and increased rates of asthma and allergies. Recent studies have added to the scope of the hypothesis, showing a link between decreased exposure to certain bacteria and parasitic worms, and increased rates of depression and intestinal auto-immune disorders, respectively. What remains less often discussed in the research on these links is that women have higher rates than men of asthma and allergies, as well as many auto-immune disorders, and also depression. The current paper introduces a feminist understanding of gender socialization to the epidemiological and immunological picture. That standards of cleanliness are generally higher for girls than boys, especially under the age of five when children are more likely to be under close adult supervision, is a robust phenomenon in industrialized nations, and some research points to a cross-cultural pattern. I conclude that, insofar as the hygiene hypothesis successfully identifies standards of hygiene and sanitation as mediators of immune health, then attention to the relevant patterns of gender socialization is important. The review also makes clear that adding a feminist analysis of gender socialization to the hygiene hypothesis helps explain variation in morbidity rates not addressed by other sources and responds to a number of outstanding puzzles in current research. Alternative explanations for the sex differences in the relevant morbidity rates are also discussed (e.g., the effects of estrogens). Finally, new sources of evidence for the hygiene hypothesis are suggested in the form of cross-cultural and other natural experiments. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Glycomarkers in parasitic infections and allergy

    Karin Hoffmann-Sommergruber, Katharina Paschinger and Iain B. H. Wilson.

    Biochemical Society transactions, Vol. 39, No. 1, 2011, pp. 360-364.

    Both helminth infections and contact with allergens result in development of a Th2 type of immune response in the affected individual. In this context, the hygiene hypothesis suggests that reduced prevalence of parasitic infections and successful vaccination strategies are causative for an increase of allergies in industrialized countries. It is therefore of interest to study glycans and their role as immunogenic structures in both parasitic infections and allergies. In the present paper we review information on the different types of glycan structure present in proteins from plant and animal food, insect venom and helminth parasites, and their role as diagnostic markers. In addition, the application of these glycan structures as immunomodulators in novel immunotherapeutic strategies is discussed.

  6. Microbial induction of immunity, inflammation, and cancer

    Julia B. Greer and Stephen John O'Keefe.

    Frontiers in physiology, Vol. PMC3059938, No. , 2011, pp. 168-168.

    The human microbiota presents a highly active metabolic that influences the state of health of our gastrointestinal tracts as well as our susceptibility to disease. Although much of our initial microbiota is adopted from our mothers, its final composition and diversity is determined by environmental factors. Westernization has significantly altered our microbial function. Extensive experimental and clinical evidence indicates that the westernized diet, rich in animal products and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, leads to a heightened inflammatory potential of the microbiota. Chronic inflammation leads to the expression of certain diseases in genetically predisposed individuals. Antibiotics and a "clean" environment, termed the "hygiene hypothesis," has been linked to the rise in allergy and inflammatory bowel disease, due to impaired beneficial bacterial exposure and education of the gut immune system, which comprises the largest immune organ within the body. The elevated risk of colon cancer is associated with the suppression of microbial fermentation and butyrate production, as butyrate provides fuel for the mucosa and is anti-inflammatory and anti-proliferative. This article will summarize the work to date highlighting the complicated and dynamic relationship between the gut microbiota and immunity, inflammation and carcinogenesis.

  7. The role of microbes in developmental immunologic programming

    Jess L. Kaplan, Hai Ning Shi and W. Allan Walker.

    Pediatric Research, Vol. 69, No. 6, 2011, pp. 465-472.

    The role of microorganisms in the gastrointestinal tract has undergone significant modification in the past few decades with new observations from clinical, epidemiologic, and basic science research. We now know that the perception of these gut microbes as pathogens or even as commensals is somewhat outdated. It is becoming increasingly clear that the gut microbiome plays an important role in a host of activities including digestion, protection from potentially pathogenic organisms, and the regulation and development of the host immune system. The complex interactions between microbes and host combined with recent clinical observations and epidemiologic trends may point to the convergence of two well-supported (though imperfect) hypotheses: the "hygiene hypothesis" and the "fetal programming hypothesis." We are beginning to understand that exposure to microbes before conception, during gestation, and in the neonatal period have profound effects on the developing immune system. Recent observations from a variety of fields help support the expansion of the "fetal programming hypothesis" to a host-microbe corollary that microbe-host interactions at critical windows influence the future immune phenotype, the maintenance of immune health, and the development of immune-mediated disease.

  8. Structural and immunologic cross-reactivity among filarial and mite tropomyosin: Implications for the hygiene hypothesis

    Helton C. Santiago, Sasisekhar Bennuru, Alexis Boyd, Mark Eberhard and Thomas B. Nutman.

    Journal of Allergy and Clinical Immunology, Vol. 127, No. 2, Feb 2011, pp. 479-486.

    Background: The hygiene hypothesis suggests that parasitic infection modulates host immune responses and decreases atopy. Other data suggest parasitic infections may induce allergic responsiveness. Objective: To assess the structural and immunologic relationships between the known Dermatophagoides pteronyssinus (Der p 10) tropomyosin allergen and filarial tropomyosin of Onchocerca volvulus (OvTrop). Methods: The molecular, structural, and immunologic relationships between OvTrop and Der p 10 were compared. Levels of OvTrop-specific and Der p 10-specific IgE, IgG, and IgG sub(4 in sera of filaria-infected and filarial-uninfected D pteronyssinus-atopic individuals were compared, as were the responses in nonhuman primates infected with the filarial parasite Loa loa. Cross-reactivity was compared by antigen-mediated depletion assays and functionality by passive basophil sensitization. Results: Filarial and mite tropomyosins were very similar, with 72% identity at the amino acid level, and overlapping predicted 3-dimensional structures. The prevalence of IgE and IgG to Der p 10 was increased in filaria-infected individuals compared with uninfected subjects. There was a strong correlation between serum levels of Ov- and Der p 10-tropomyosin - specific IgE, IgG, and IgG) sub(4) (P 0.79). Preincubation of sera from anti-Der p 10 - positive subjects with OvTrop completely depleted IgE, IgG, and IgG sub(4 anti-Der p 10. Basophils sensitized with sera from individuals allergic to Der p 10 released histamine similarly when triggered with OvTrop or Der p 10. Primates experimentally infected with L loa developed IgE that cross-reacted with Der p 10. Conclusion: Filarial infection induces strong cross-reactive antitropomyosin antibody responses that may affect sensitization and regulation of allergic reactivity.)

  9. The allergy-protective properties of Acinetobacter lwoffii F78 are imparted by its lipopolysaccharide

    J. Debarry, A. Hanuszkiewicz, K. Stein, O. Holst and H. Heine.

    Allergy, Vol. 65, No. 6, Jun 2010, pp. 690-697.

    Background: An increasing number of epidemiological studies show that exposure to farming environment during early childhood strongly influences the development of allergic reactions later in life ('hygiene hypothesis'). Also, it had been shown that certain bacteria from this environment may have allergy-protective properties. In the present study, we further characterized one of these bacteria, namely Acinetobacter lwoffii F78, with regard to the bacteria-induced signaling and possible mechanisms of allergy protection.Methods: The impact of A. lwoffii F78 on human monocyte-derived dendritic cells especially with respect to their THelper cell polarization capacity was investigated by ELISA and real-time PCR experiments as well as confocal microscopy. The responsible molecule for these effects was further characterized and identified using blocking experiments.Results: It was shown that A. lwoffii F78 induced a TH1-polarizing program in human dendritic cells which led to TH1 differentiation. In addition, a positive influence on the TBet-GATA3 level could be detected. Blocking experiments revealed that the lipopolysaccharide (LPS) of A. lwoffii F78 was the responsible molecule promoting these effects.Conclusion: We found evidence that the allergy-protecting effects of A. lwoffii F78 are because of the activation of a TH1-polarizing program in human dendritic cells, and that the LPS of A. lwoffii F78 is responsible for these beneficial effects.

  10. Asthma in late adolescence – farm childhood is protective and the prevalence increase has levelled off

    Goeran Wennergren, Linda Ekerljung, Bernt Alm, Jonas Eriksson, Jan Loetvall and Bo Lundbaeck.

    Pediatric Allergy and Immunology, Vol. 21, No. 5, Aug 2010, pp. 806-813.

    While the prevalence of and risk factors for asthma in childhood have been studied extensively, the data for late adolescence are more sparse. The aim of this study was to provide up-to-date information on the prevalence of and risk factors for asthma in the transitional period between childhood and adulthood. A secondary aim was to analyze whether the increase in asthma prevalence has levelled off. A large-scale, detailed postal questionnaire focusing on asthma and respiratory symptoms, as well as possible risk factors, was mailed to 30 000 randomly selected subjects aged 16-75 in Gothenburg and the surrounding western Sweden region. The present analyses are based on the responses from 1261 subjects aged 16-20 (560 men and 701 women). The prevalence of physician-diagnosed asthma was 9.5%, while 9.6% reported the use of asthma medicine. In the multivariate analysis, the strongest risk factors for physician-diagnosed asthma and other asthma variables were heredity for asthma and heredity for allergy, particularly if they occurred together. Growing up on a farm significantly reduced the prevalence of physician-diagnosed asthma and the likelihood of using asthma medication, OR 0.1 (95% CI 0.02-0.95). Smoking increased the risk of recurrent wheeze, long-standing cough, and sputum production. In conclusion, the prevalence of physician-diagnosed asthma and the use of asthma medication in the 16- to 20-yr age group support the notion that the increase in asthma prevalence seen between the 1950s and the 1990s has now levelled off. In line with the hygiene hypothesis, a farm childhood significantly reduced the likelihood of asthma. The adverse effects of smoking could already be seen at this young age.

  11. Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics

    Marko Kalliomäki, Jean-Michel Antoine, Udo Herz, Ger T. Rijkers, Jerry M. Wells and Annick Mercenier.

    The Journal of nutrition, Vol. 140, No. 3, 2010, pp. 713S-21S.

    Allergy is a hypersensitivity reaction mediated by specific antibody-mediated or cell-mediated immunologic mechanisms and clinically manifested as atopic eczema, allergic rhinoconjunctivitis, or asthma. During the recent decades there has been an increase in allergy prevalence, which is attributed to changes in environmental factors. The so-called "hygiene hypothesis" suggests that a lack of exposure to microbial stimulus early in childhood is a major factor involved in this trend. This provides a rationale for using probiotics to modify the gut microbiota and thereby shaping the immune response of the host, especially in infancy. Most success has been obtained in primary prevention of atopic eczema. A limited number of studies also provided evidence for a beneficial effect of different probiotics in the management of allergic diseases (atopic eczema, allergic rhinitis). However, choice of probiotic strains as well as timing of the intervention are important variables. The exact in vivo mechanism of probiotics in shaping the immune response still needs to be determined. Future studies should use uniform criteria for diagnosis and symptom scoring of atopic diseases and may identify the genes predisposing to allergic disease. There is encouraging evidence that specific probiotics can become valuable tools in the prevention and management of allergic diseases.

  12. Helminth infection inhibits airway allergic reaction and dendritic cells are involved in the modulation process

    P. LIU, J. LI, X. YANG, et al.

    Parasite immunology, Vol. 32, No. 1, Jan 2010, pp. 57-66.

    Several previous studies have demonstrated that some helminth infections can inhibit allergic reactions, but the examination on the effect of live Schistosoma japonicum (SJ) infection on allergic inflammation remains limited. The aim of this study was to examine the effect and mechanism of chronic SJ infection on airway allergic inflammation in a murine model. The data showed that chronic SJ infection suppressed airway eosinophilia, mucus production and antigen-specific IgE responses induced by ovalbumin (OVA) sensitization and challenge. Cytokine production analysis showed that chronic SJ infection reduced allergen-driven interleukin (IL)-4 and IL-5 production, but had no significant effect on IFN-γ production. More importantly, we found that the adoptive transfer of dendritic cells (DCs) from SJ-infected mice dramatically decreased airway allergic inflammation in the recipients, which was associated with significant decrease of IL-4/IL-5 production and increase of IL-10 production. The results suggest that SJ infection may inhibit the development of allergy and that DCs may be involved in the process of helminth infection-mediated modulation of allergic inflammation.

  13. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update

    H. Okada, C. Kuhn, H. Feillet and J-F Bach.

    Clinical and experimental immunology, Vol. 160, No. 1, Apr 2010, pp. 1-9.

    SummaryAccording to the 'hygiene hypothesis', the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both autoimmune and allergic diseases. The hygiene hypothesis is based upon epidemiological data, particularly migration studies, showing that subjects migrating from a low-incidence to a high-incidence country acquire the immune disorders with a high incidence at the first generation. However, these data and others showing a correlation between high disease incidence and high socio-economic level do not prove a causal link between infections and immune disorders. Proof of principle of the hygiene hypothesis is brought by animal models and to a lesser degree by intervention trials in humans. Underlying mechanisms are multiple and complex. They include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These mechanisms could originate, to some extent, from changes in microbiota caused by changes in lifestyle, particularly in inflammatory bowel diseases. Taken together, these data open new therapeutic perspectives in the prevention of autoimmune and allergic diseases.

  14. The hygiene hypothesis revisited: role of materno-fetal interactions

    Catherine A. Thornton, Trisha V. Macfarlane and Patrick G. Holt.

    Current allergy and asthma reports, Vol. 10, No. 6, 2010, pp. 444-452.

    For 20 years, the hygiene hypothesis has dominated attempts to explain the increasing prevalence of allergic disease. A causal link between maternal innate immune response during pregnancy and disease protection in the offspring was recently demonstrated. Central to this was a systemically diffused signal that downregulated Toll-like receptor expression in placental tissues. Herein we develop the hypothesis that maternal systemic regulatory mechanisms operational during pregnancy could impact allergic disease risk of the offspring, depending on the type of inflammatory response from which they originate. Classic microbial-derived, mild, subacute inflammation provides a protective signal, whereas allergic inflammation provides a negative one. Mild, subacute inflammation of pregnant women leads to systemically diffused signals manifest in the gestation-associated tissues and by the fetus and newborn as a dampened inflammatory response. The converse is true if the mother has allergic inflammation during pregnancy. In both cases, these impact on development of the airways and of balanced immune function at birth and in early postnatal life. Thus, we seem to be at the dawn of a new incarnation of the hygiene hypothesis in which the pregnant woman's inflammatory response is crucial to determining the child's likelihood of developing allergic disease.

  15. The hygiene hypothesis: an evolutionary perspective

    Manuela Sironi and Mario Clerici.

    Microbes and infection / Institut Pasteur, Vol. 12, No. 6, 2010, pp. 421-427.

    The hygiene hypothesis relies on the assumption that humans have adapted to a pathogen-rich environment that no longer exists in industrialized societies. Recent advances in molecular immunology and population genetics allow deeper insight into the evolution and co-evolution of host-pathogen interactions and, therefore, into the foundations of the hygiene hypothesis.Copyright 2010 Elsevier Masson SAS. All rights reserved.

  16. Hygiene hypothesis: wanted—dead or alive

    Allan Linneberg.

    International journal of epidemiology, Vol. 39, No. 1, 2010, pp. 313-4; author reply 314-7.

    The hygiene hypothesis is an intriguing attempt to explain the rise in allergy and asthma (and other immunological diseases) in populations undergoing changes in the environment towards increasing cleanliness, use of vaccinations and antibiotics, lower rates of infections, etc. In many ways this idea is appealing and seems to offer a unifying explanation of many epidemiological observations. However, in a recent issue of the IJE, Douwes and Pearce summarize different controversies relating to the hygiene hypo-thesis in their commentary on the observed recent decrease in asthma in Australia. As pointed out by Douwes and Pearce, recent downward trends of asthma/allergy prevalence reported in some countries seem unlikely to be explained by a decrease in hygiene and they conclude that new aetiological theories may be required.

  17. The immunology of human hookworm infections

    H. J. McSORLEY and A. LOUKAS.

    Parasite immunology, Vol. 32, No. 8, Aug 2010, pp. 549-559.

    Hookworms are one of the most prevalent parasites of humans in developing countries, but we know relatively little about the immune response generated to hookworm infection. This can be attributed to a lack of permissive animal models and a relatively small research community compared with those of the more high-profile parasitic diseases. However, recently, research has emerged on the development of vaccines to control hookworm infection and the use of hookworm to treat autoimmune and allergic disorders, contributing to a greater understanding of the strategies used by hookworms to modulate the host's immune response. A substantial body of research on the immunobiology of hookworms originates from Australia, so this review will summarize the current status of the field with a particular emphasis on research carried out 'down under'.

  18. Immunomodulating effects of endotoxin in mouse models of allergic asthma

    Z. Zhu, SY Oh, T. Zheng and Y-K Kim.

    Clinical and Experimental Allergy, Vol. 40, No. 4, Apr 2010, pp. 536-546.

    SummaryEndotoxin or lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria. Like aeroallergens, LPS is ubiquitous in our living environment. Epidemiology studies in young children have found that LPS exposure at home is inversely correlated with the development of atopic diseases, thus the 'hygiene hypothesis' for allergic diseases. However, positive association has also been found between indoor LPS exposure and the development of wheezing or asthma in children. In humans, experimental exposure to LPS in the airways can cause inflammatory responses and lung function changes directly or modulate responses to allergens indirectly, particularly in those with asthma. In animal studies, experimental exposure to LPS has generated some conflicting, sometimes opposite, results in host responses to allergen stimulation. In this article, we will review recent advances in our understanding of the immunomodulating effects of LPS on allergen-induced responses and analyse some of the possible reasons for the inconsistent findings.

  19. Inflammation, sanitation, and consternation: loss of contact with coevolved, tolerogenic microorganisms and the pathophysiology and treatment of major depression

    Charles L. Raison, Christopher A. Lowry and Graham A. W. Rook.

    Archives of General Psychiatry, Vol. 67, No. 12, 2010, pp. 1211-1224.

    Inflammation is increasingly recognized as contributing to the pathogenesis of major depressive disorder (MDD), even in individuals who are otherwise medically healthy. Most studies in search of sources for this increased inflammation have focused on factors such as psychosocial stress and obesity that are known to activate inflammatory processes and increase the risk for depression. However, MDD may be so prevalent in the modern world not just because proinflammatory factors are widespread, but also because we have lost contact with previously available sources of anti-inflammatory, immunoregulatory signaling.To examine evidence that disruptions in coevolved relationships with a variety of tolerogenic microorganisms that were previously ubiquitous in soil, food, and the gut, but that are largely missing from industrialized societies, may contribute to increasing rates of MDD in the modern world.Relevant studies were identified using PubMed and Ovid MEDLINE.Included were laboratory animal and human studies relevant to immune functioning, the hygiene hypothesis, and major depressive disorder identified via PubMed and Ovid MEDLINE searches.Studies were reviewed by all authors, and data considered to be potentially relevant to the contribution of hygiene-related immune variables to major depressive disorder were extracted.Significant data suggest that a variety of microorganisms (frequently referred to as the "old friends") were tasked by coevolutionary processes with training the human immune system to tolerate a wide array of non-threatening but potentially proinflammatory stimuli. Lacking such immune training, vulnerable individuals in the modern world are at significantly increased risk of mounting inappropriate inflammatory attacks on harmless environmental antigens (leading to asthma), benign food contents and commensals in the gut (leading to inflammatory bowel disease), or self-antigens (leading to any of a host of autoimmune diseases). Loss of exposure to the old friends may promote MDD by increasing background levels of depressogenic cytokines and may predispose vulnerable individuals in industrialized societies to mount inappropriately aggressive inflammatory responses to psychosocial stressors, again leading to increased rates of depression.Measured exposure to the old friends or their antigens may offer promise for the prevention and treatment of MDD in modern industrialized societies.

  20. Is there a rural-urban gradient in the prevalence of eczema? A systematic review

    ME Schram, AM Tedja, R. Spijker, JD Bos, HC Williams and PhI Spuls.

    British Journal of Dermatology, Vol. 162, No. 5, May 2010, pp. 964-973.

    SummaryBackground Eczema affects approximately 10% of all schoolchildren in the western world and has shown an increase over the past decades in 'developing' countries. Numerous factors have been suggested that might contribute to the increasing prevalence of eczema. A plausible explanation is the role of environmental factors. As part of the 'hygiene hypothesis' it has been thought that eczema is more common in urban than in rural communities, but such a notion has never been assessed systematically.Objective Our aim was to assess whether there is a rural-urban gradient for the prevalence of eczema and, if so, to what extent.Methods All data sources were identified through a search in MEDLINE and EMBASE. All primary studies comparing the prevalence rate of eczema between urban and rural populations were assessed for eligibility. Included articles were reviewed for methodological quality and a relative risk was calculated to indicate the risk of eczema in urban over rural areas.Results Twenty-six articles were included for analysis. Nineteen showed a higher risk for eczema in an urbanized area, of which 11 were significant. Six studies showed a lower risk of eczema in an urbanized area, of which one was statistically significant. One study had a relative risk of 1.00. Results were more homogeneous among studies of good methodological quality. A pooled relative risk could have been calculated but was not because of heterogeneity.Conclusion There is some evidence of a higher risk for eczema in urban compared with rural areas, suggesting that place of residence may have a role in the pathogenesis of eczema. Future reviews on environmental circumstances should be carried out to reveal the factors associated with a higher prevalence of eczema in urban areas and the association with other allergic diseases.

  21. Microbe-host interaction in chronic diseases

    Dirk Haller and Ingo B. Autenrieth.

    International Journal of Medical Microbiology, Vol. 300, No. 1, Jan 2010, pp. 1-2.

    The increasing incidence of chronic degenerative and "lifestyle-dependent" diseases implies a complex interaction of genetic predispositions and environmental factors. Immunity and metabolism co-evolved under the evolutionary pressure of pathogenic microorganisms and limited nutritional resources. Emerging evidence suggests that the decline of infectious disease, in combination with the sedentary lifestyle of an overfed population, may lead to the development of metabolically-driven and inflammation-mediated pathologies including obesity-associated co-morbidities such as diabetes as well as autoimmune and allergic disorders such as inflammatory bowel disease, atopic dermatitis, and asthma. The hygiene hypothesis provides a challenging concept for the explanation of increases in chronic inflammatory diseases. In this regard the complex gut-associated microbial ecosystem (gut microbiota) and nutrition-related factors are the most important environmental triggers for the development and modification of these lifestyle-related diseases. The gut with its large mucosal surface acts hereby as a highly selective barrier and communication organ between the environmental factors and the immune system responsible for the regulation of metabolic and immune functions. It has even been proposed to complement the search for disease susceptibility genes in the human genome with the analysis of the gut "microbiome", considering the fact that health or disease is being determined by the complex interaction of the host with its gut microbial ecosystem. The coexistence of a microbial ecosystem within the host is tightly controlled at various levels and an accumulating body of evidence suggests that the failure of this homeostasis is an important contribution to disease development affecting fat storage and type-2 diabetes as well as autoimmune type-1 diabetes and inflammatory bowel diseases. Thus, a strong and growing body of evidence shows that the gut microbiota as well as nutritional factors and the metabolic status of individuals throughout their lifespan are powerful determinants of chronic diseases, and that the underlying mechanisms involve the development of inflammatory activity in the intestinal mucosa. The German Society for Hygiene and Microbiology (DGHM) has established a new section " Microbiota, Probiota and Host" aiming to integrate a panel of multidisciplinary experts relevant to novel aspects in microbiology, immunology gastroenterology and nutrition science. Cutting-edge technologies such as transcriptomics, proteomics and metabolomics should be implemented in the compositional and functional analysis of the gut microbiota, host metabolism and immunity as well as pre- and probiotic mechanisms. This new platform should enable cross-sectional discussions in the understanding of the role of bacteria-host interactions in the development or prevention of modern pathologies including chronic inflammatory, atopic and metabolic diseases. The articles put together in this special issue of the International Journal of Medical Microbiology were in part presented at the first international meeting in May 2008 at Kloster Seeon in Germany organized by the new DGHM section "Microbiota, Probiota and Host".

  22. Microbial exposure early in life regulates airway inflammation in mice after infection with Streptococcus pneumoniae with enhancement of local resistance

    Yasuki Yasuda, Yoko Matsumura, Kazuki Kasahara, et al.

    American journal of physiology.Lung cellular and molecular physiology, Vol. 298, No. 1, 2010, pp. L67-L78.

    The immunological explanation for the "hygiene hypothesis" has been proposed to be induction of T helper 1 (Th1) responses by microbial products. However, the protective results of hygiene hypothesis-linked microbial exposures are currently shown to be unlikely to result from a Th1-skewed response. Until now, effect of microbial exposure early in life on airway innate resistance remained unclear. We examined the role of early life exposure to microbes in airway innate resistance to a respiratory pathogen. Specific pathogen-free weanling mice were nasally exposed to the mixture of microbial extracts or PBS (control) every other day for 28 days and intratracheally infected with Streptococcus pneumoniae 10 days after the last exposure. Exposure to microbial extracts facilitated colonization of aerobic gram-positive bacteria, anaerobic microorganisms, and Lactobacillus in the airway, compared with control exposure. In pneumococcal pneumonia, the exposure prolonged mouse survival days by suppressing bacterial growth and by retarding pneumococcal blood invasion, despite significantly low levels of leukocyte recruitment in the lung. Enhancement of airway resistance was associated with a significant decrease in production of leukocyte chemokine (KC) and TNFalpha, and suppression of matrix metalloproteinase (MMP-9) expression/activation with enhancement of tissue inhibitor of MMP (TIMP-3) activation. The exposure increased production of IFN-gamma, IL-4, and monocyte chemoattractant-1 following infection. Furthermore, expression of Toll-like receptor 2, 4, and 9 was promoted by the exposure but no longer upregulated upon pneumococcal infection. Thus, we suggest that hygiene hypothesis is more important in regulating the PMN-dominant inflammatory response than in inducing a Th1-dominant response.

  23. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded?

    Giovanni Musso, Roberto Gambino and Maurizio Cassader.

    Diabetes care, Vol. PMC2945175, No. 10, 2010, pp. 2277-2284.

    The connection between gut microbiota and energy homeostasis and inflammation and its role in the pathogenesis of obesity-related disorders are increasingly recognized. Animals models of obesity connect an altered microbiota composition to the development of obesity, insulin resistance, and diabetes in the host through several mechanisms: increased energy harvest from the diet, altered fatty acid metabolism and composition in adipose tissue and liver, modulation of gut peptide YY and glucagon-like peptide (GLP)-1 secretion, activation of the lipopolysaccharide toll-like receptor-4 axis, and modulation of intestinal barrier integrity by GLP-2. Instrumental for gut microbiota manipulation is the understanding of mechanisms regulating gut microbiota composition. Several factors shape the gut microflora during infancy: mode of delivery, type of infant feeding, hospitalization, and prematurity. Furthermore, the key importance of antibiotic use and dietary nutrient composition are increasingly recognized. The role of the Western diet in promoting an obesogenic gut microbiota is being confirmation in subjects. Following encouraging results in animals, several short-term randomized controlled trials showed the benefit of prebiotics and probiotics on insulin sensitivity, inflammatory markers, postprandial incretins, and glucose tolerance. Future research is needed to unravel the hormonal, immunomodulatory, and metabolic mechanisms underlying microbe-microbe and microbiota-host interactions and the specific genes that determine the health benefit derived from probiotics. While awaiting further randomized trials assessing long-term safety and benefits on clinical end points, a healthy lifestyle—including breast lactation, appropriate antibiotic use, and the avoidance of excessive dietary fat intake—may ensure a friendly gut microbiota and positively affect prevention and treatment of metabolic disorders.

  24. Parasitic Helminths: New Weapons against Immunological Disorders

    Yoshio Osada and Tamotsu Kanazawa.

    Journal of Biomedicine and Biotechnology, Vol. 2010, [np].

    The prevalence of allergic and autoimmune diseases is increasing in developed countries, possibly due to reduced exposure to microorganisms in childhood (hygiene hypothesis). Epidemiological and experimental evidence in support of this hypothesis is accumulating. In this context, parasitic helminths are now important candidates for antiallergic/anti-inflammatory agents. Here we summarize antiallergic/anti-inflammatory effects of helminths together along with our own study of the effects of Schistosoma mansoni on Th17-dependent experimental arthritis. We also discuss possible mechanisms of helminth-induced suppression according to the recent advances of immunology.

  25. Probiotics and allergy in children - An update review

    Shih-Jin Pan, Chang-Hung Kuo, Ka-Pan Lam, Yu-Te Chu, Wei-Li Wang and Chih-Hsing Hung.

    Pediatric Allergy and Immunology, Vol. 21, No. 4p2, Jun 2010, pp. e659-e666.

    The hygiene hypothesis suggests that the increased prevalence of allergic diseases has resulted from a relative lack of microbial stimuli during infancy and early childhood. Children with atopic diseases have different commensal bacterial groups in the gut compared to non-atopic children, and differences are also found between countries with high and low incidence of atopic diseases. Probiotics are defined as live microorganisms that provide benefits to the health of a host by altering the host's microflora when they are administered in adequate amounts. They are being investigated for possible roles in managing allergic diseases. To date, the evidence that probiotics can be used to treat or prevent allergic diseases of children remains controversial. We reviewed recent randomized, double-blinded, placebo-controlled clinical trials using probiotics for allergic diseases of children and evaluated their clinical efficacy, possible mechanisms, dosage, and safety for managing allergic diseases of children. The current data are insufficient to strongly recommend probiotics as a standard treatment or preventative measure for pediatric allergic disease. More studies are needed to standardize study designs, bacterial strains, dosages, and durations for different allergic diseases of children.

  26. Probiotics for allergic respiratory diseases – Putting it into perspective

    Meenu Singh and Rashmi Ranjan Das.

    Pediatric Allergy and Immunology, Vol. 21, No. 2p2, Mar 2010, pp. e368-e376.

    Respiratory allergies include allergic rhinitis, sinusitis and asthma. Increasing attention on pathogenesis of allergic airway diseases has given rise to 'atopic march' hypothesis i.e. clinical features of atopic eczema occur first and precede the development of asthma and allergic rhinitis. The 'hygiene hypothesis' proposes that the increase in allergic diseases reflects a decrease in infections during childhood. Clinical trials also suggest that the exposure to microbes through the gastrointestinal tract powerfully shapes immune function. Probiotics are live organisms which exert a beneficial effect in the prevention as well as treatment of allergic diseases through modification of immune system of host via gut ecosystem. Intestinal microbiota differs in infants who later develop allergic diseases, and feeding probiotics to infants at risk has been shown to reduce their rate of developing eczema. This has prompted studies of feeding probiotics in prevention as well as treatment of respiratory allergy. We hereby discuss the status of probiotics in respiratory allergy.

  27. Role of dendritic cells: a step forward for the hygiene hypothesis

    Xi Yang and Xiaoling Gao.

    Cellular & molecular immunology, Vol. 8, No. 1, 2010, pp. 12-18.

    The hygiene hypothesis was proposed more than two decades ago, but its mechanism remains unclear. This review focuses on recent advances in the field, especially on the role played by dendritic cells (DCs) and their modulating effects on various infections and allergic diseases, including allergic asthma. DCs isolated from mice long after the resolution of an infection were reported to have a significant modulating effect on allergen-specific Th2 responses in both in vitro and in vivo systems. These DCs showed DC1-like and/or tolerogenic DC capacity, which allowed for the inhibition of allergic responses by immune deviation (enhancing Th1 response) and immune regulation (through regulatory T-cell and Th2 hyporesponsiveness) mechanisms. These findings represented a significant advance in the elucidation of the mechanisms underlying the hygiene hypothesis. Further investigation on the mechanisms by which DCs are 'educated' by infectious agents and the influence of the type, time, and extent of infections on this 'education' process will help us understand immune regulation in disease settings and in the rational design of preventive/therapeutic approaches to allergy/asthma and infections.

  28. The suppression of immune system disorders by passive attrition

    Sean P. Stromberg and Jean M. Carlson.

    PloS one, Vol. PMC2838783, No. 3, 2010, pp. e9648-e9648.

    Exposure to infectious diseases has an unexpected benefit of inhibiting autoimmune diseases and allergies. This is one of many fundamental fitness tradeoffs associated with immune system architecture. The immune system attacks pathogens, but also may (inappropriately) attack the host. Exposure to pathogens can suppress the deleterious response, at the price of illness and the decay of immunity to previous diseases. This "hygiene hypothesis" has been associated with several possible underlying biological mechanisms. This study focuses on physiological constraints that lead to competition for survival between immune system cell types. Competition maintains a relatively constant total number of cells within each niche. The constraint implies that adding cells conferring new immunity requires loss (passive attrition) of some cells conferring previous immunities. We consider passive attrition as a mechanism to prevent the initial proliferation of autoreactive cells, thus preventing autoimmune disease. We see that this protection is a general property of homeostatic regulation and we look specifically at both the IL-15 and IL-7 regulated niches to make quantitative predictions using a mathematical model. This mathematical model yields insight into the dynamics of the "Hygiene Hypothesis," and makes quantitative predictions for experiments testing the ability of passive attrition to suppress immune system disorders. The model also makes a prediction of an anti-correlation between prevalence of immune system disorders and passive attrition rates.

  29. Exploring the immunology of parasitism – from surface antigens to the hygiene hypothesis

    RM MAIZELS.

    Parasitology, Vol. 136, No. 12, Oct 2009, pp. 1549-1564.

    Helminth immunology is a field which has changed beyond recognition in the past 30 years, transformed not only by new technologies from cDNA cloning to flow cytometry, but also conceptually as our definition of host immune pathways has matured. The molecular revolution defined key nematode surface and secreted antigens, and identified candidate immunomodulators that are likely to underpin parasites' success in eluding immune attack. The immunological advances in defining cytokine networks, lymphocyte subsets and innate cell recognition have also made a huge impact on our understanding of helminth infections. Most recently, the ideas of regulatory immune cells, in particular the regulatory T cell, have again overturned older thinking, but also may explain immune hyporesponsiveness observed in chronic helminth diseases, as well as the link to reduced allergic reactions observed in human and animal infections. The review concludes with a forward look to where we may make future advances towards the final eradication of helminth diseases.

  30. Practical prebiotics, probiotics and synbiotics for allergists: how useful are they?

    H. Johannsen and S. L. Prescott.

    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, Vol. 39, No. 12, 2009, pp. 1801-1814.

    With the advent of the hygiene hypothesis, probiotics have provided an avenue of hope in curbing the allergic epidemic. The initial enthusiasm has been tempered by recognition of the inherent complexities of this approach. This review examines the current clinical evidence and practical issues in using probiotics and related products, for the prevention and treatment of allergic disease. So far, probiotics have shown more promise, albeit limited, in the primary prevention of allergic disease rather than in the treatment of established disease. These effects have largely been limited to the prevention of early childhood conditions such as eczema, with no consistent effects on other allergic outcomes. There is emerging evidence that clinical effects may be strain specific, but again these findings have been inconsistent. While there have been several meta-analyses to examine probiotics in both the prevention and the treatment of allergic disease, these have been hampered by significant heterogeneity between studies, including wide variations in the strains used, the methods and timing of administration and the age and assessment of allergic outcomes. In any case, these have also become outdated by a series of new studies published in the last year. Although it is not yet clear exactly how the growing number of new studies will modify the results of meta-analyses, it is likely that these will add yet further heterogeneity that will continue to make interpretation of pooled data difficult. At this stage, the effects of prebiotics, synbiotics and postbiotics are even less clear. Thus, while there is little doubt that microbiota modulate immune development and can prevent the allergic phenotype, the optimal way of achieving this is far from clear. Given the current level of evidence, it is not appropriate to recommend prebiotics/probiotics/synbiotics or postbiotics as a part of standard therapy or for the prevention of any allergic conditions. Further studies are needed to address the growing speculation that supplementation with a single probiotic strain may be oversimplistic and that approaches that have a more global effect on colonization may be warranted.

  31. Recent findings on the pathogenesis of bronchial asthma. Part II. The role of hormonal predisposition, environmental influences and conditioning leading to bronchial asthma

    József Iván Székely and A. Pataki.

    Acta Physiologica Hungarica, Vol. 96, No. 3, 2009, pp. 289-305.

    In this second part of the review on the pathogenesis of asthma the hormonal factors and adverse external events are shortly reviewed which skew the balance of Th1 vs. Th2 CD4+ lymphocytes towards the latter ones and this way increase the probability of atopic diseases. Among other the role of transplacental priming, insulin, insulin-like and other growth factors, lack of the usual microbial infections in the early childhood (the so-called hygiene hypothesis), gender, diminished testosterone production, gastroesophageal reflux, adverse effects during pregnancy are discussed. A separate chapter deals with the role of central nervous system in the etiology and finally the most common allergizing and airway tissue damaging agents are listed in tabulated form.

  32. Structural and Immunologic Cross Reactivity among Allergens and Homologous Helminth Antigens: Lessons Learned from Tropomyosin and Their Implication for the Hygiene Hypothesis

    Helton Santiago, Sasisekhar Bennuru and Thomas Nutman.

    58th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Washington, D. C., U.S.A., 2009.

    With allergy increasing in both resource-rich and -poor countries and with the mechanisms underlying this increase being multi-factorial and poorly understood, it has been suggested that the relationship between allergy and control of helminth infection is the major determinant (socalled "Hygiene hypothesis"). Nevertheless, there are data to show that helminth infection can aggravate or induce allergic reactivity. To address specifically the relationship between the structure of particular helminth antigens and their important homologues among known allergens, we assessed the immunological cross-reactivity of parasite and non-parasite tropomyosin, as tropomyosin is an important allergen that is common to a variety of organisms including crustaceans, mites and cockroach. To this end, tropomyosins from Onchocerca volvulus (Ov) and Dermatophagoids pteronyssius (Der p) were assessed for reactivity of IgE and IgG antibodies in 58 individuals with helminth infection and 21 non-infected individuals allergic to house dust mite. Our data showed a strong correlation between serum levels of both for tropomyosin-specific IgE and IgG (p<0.0001, r=0.97). Pre-incubation of sera from Der p allergic patients with Ov tropomyosin depleted IgE and IgG anti-Der p tropomyosin by 100 percent when compared to pre-incubation with Der p tropomyosin itself. Moreover, Ov-tropomysin inhibited the binding of Der p-specific antibodies to Der p tropomyosin using an interference ELISA, whereas an unrelated antigen failed to inhibit at all. Taken together, our data suggest a strong cross reactivity between Der p and Ov tropomyosin that may provide insight into the relationship between helminths and allergic disease.