Associations of Helicobacter pylori and hepatitis A seropositivity with asthma in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): addressing the hygiene hypothesis

Background The hygiene hypothesis posits that microbial exposure reduces risk of asthma and other respiratory-related diseases. Helicobacter pylori and hepatitis A virus (HAV) are common fecal–oral infections. Our study aimed to examine associations of seropositivity to these agents with asthma in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods A total of 12,471 HCHS/SOL participants with baseline data on self-reported physician-diagnosed asthma, and antibodies anti-H. pylori and anti-HAV were included in this cross-sectional analysis. Multivariable logistic regression models were used to estimate the odds ratios and 95% confidence intervals for the overall associations of seropositivity to each agent with asthma. Analyses were also stratified by Hispanic/Latino background. Effect modification by smoking status and nativity were tested. An analysis restricted to individuals with spirometry-defined chronic obstructive pulmonary disease (COPD) was also considered. Results The weighted overall prevalence of asthma was 16.6%. The weighted seroprevalence of H. pylori was 56.6% and of HAV was 76.6%, and they significantly differed by Hispanic/Latino background. After accounting for age, sex, education and other key confounders, we found no associations between H. pylori or HAV seropositivity with asthma (with and without COPD), either for all individuals combined or for any of the six specific backgrounds. There were no significant interactions by smoking and nativity. Conclusion Our findings did not provide support for the role of H. pylori or HAV, as evidence of the hygiene hypothesis in asthma among the large and diverse Hispanic/Latino populations of the HCHS/SOL. Trial registration NCT02060344

Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development

Kawasaki disease (KD) is an acute systemic vasculitis that occurs predominantly in children under 5 years of age. Despite much study, the etiology of KD remains unknown. However, epidemiological and immunological data support the hygiene hypothesis as a possible etiology. It is thought that more sterile or clean modern living environments due to increased use of sanitizing agents, antibiotics, and formula feeding result in a lack of immunological challenges, leading to defective or dysregulated B cell development, accompanied by low IgG and high IgE levels. A lack of B cell immunity may increase sensitivity to unknown environmental triggers that are nonpathogenic in healthy individuals. Genetic studies of KD show that all of the KD susceptibility genes identified by genome-wide association studies are involved in B cell development and function, particularly in early B cell development (from the pro-B to pre-B cell stage). The fact that intravenous immunoglobulin is an effective therapy for KD supports this hypothesis. In this review, I discuss clinical, epidemiological, immunological, and genetic studies showing that the etiopathogenesis of KD in infants and toddlers can be explained by the hygiene hypothesis, and particularly by defects or dysregulation during early B cell development.

Hygiene hypothesis and occupational asthma to vegetable textile dusts: A pilot study

Background: Over the last decades, the prevalence of allergic manifestations has increased significantly. To explain the increase in the prevalence of asthma, Strachan advanced the Hygiene Hypothesis, which states that decreased exposure to infectious microorganisms in infancy may have contributed to changes in the maturation of the immune system during childhood. To the best of our knowledge, no analytical studies detailing the links between the Hygiene Hypothesis and occupational allergy have been carried out to date. Objective: To study the relations between the factors involved in the Hygiene Hypothesis and the occurrence of occupational asthma (OA) to vegetable textile dusts. Methods: A case-control study was conducted from September 2017 to September 2018. The cases and controls were enrolled from the occupational medicine department of the University Hospital “Farhat Hached” of Sousse (Tunisia) among patients attending from 2009 to 2016. The case group was composed of patients diagnosed with OA to vegetable textile dusts. Controls were age and gender matched, working in the textile sector and not suffering from any allergic diseases. Results: A total of 57 OA cases and 112 controls were enrolled. Four factors involved in the Hygiene Hypothesis were independently associated with OA to vegetable textile dusts: the lowest rank in siblings (p=0.037; ORa=0.14; 95% CI= [0.02-0.90]); contact with animals (p=0.006; ORa=0.22; 95% CI= [0.08-0.65]) especially cats; history of parasitic and/or mycotic infections in childhood (p=0.004; ORa=0.035; 95% CI= [0.004-0.35]) and history of viral infections in childhood (p<10-3; ORa=0.028; 95% CI= [0.01-0.14]). Other factors had a protective effect, such as the parents' low socioeconomic level and the father's occupation as a farmer. Conclusion: The microorganism-rich environment during childhood is an important model for understanding the mechanisms involved in the development of allergic asthma. Our data suggest that prevention of OA in adults might require early intervention in childhood.

Mycobacterium-Induced Th1, Helminths-Induced Th2 Cells and the Potential Vaccine Candidates for Allergic Asthma: Imitation of Natural Infection

Bronchial asthma is one of the most chronic pulmonary diseases and major public health problems. In general, asthma prevails in developed countries than developing countries, and its prevalence is increasing in the latter. For instance, the hygiene hypothesis demonstrated that this phenomenon resulted from higher household hygienic standards that decreased the chances of infections, which would subsequently increase the occurrence of allergy. In this review, we attempted to integrate our knowledge with the hygiene hypothesis into beneficial preventive approaches for allergic asthma. Therefore, we highlighted the studies that investigated the correlation between allergic asthma and the two different types of infections that induce the two major antagonizing arms of T cells. This elucidation reflects the association between various types of natural infections and the immune system, which is predicted to support the main objective of the current research on investigating of the benefits of natural infections, regardless their immune pathways for the prevention of allergic asthma. We demonstrated that natural infection with Mycobacterium tuberculosis (Mtb) prevents the development of allergic asthma, thus Bacille Calmette-Guérin (BCG) vaccine is suggested at early age to mediate the same prevention particularly with increasing its efficiency through genetic engineering-based modifications. Likewise, natural helminth infections might inhabit the allergic asthma development. Therefore, helminth-derived proteins at early age are good candidates for designing vaccines for allergic asthma and it requires further investigation. Finally, we recommend imitation of natural infections as a general strategy for preventing allergic asthma that increased dramatically over the past decades.

Laboratory mice with a wild microbiota generate strong allergic immune responses

Allergic disorders are caused by a combination of hereditary and environmental factors. The hygiene hypothesis postulates that early life microbial exposures impede the development of subsequent allergic disease. However, unambiguous evidence that microbes reduce the development of allergic disorders is still lacking. Recently developed wildling mice contain a rich and diverse commensal and encounter a repertoire of microbes typical of the wild, with pathogenic potential. Here, we probed the hygiene hypothesis by comparing the development of allergic inflammation in wildlings to that of genetically identical mice lacking diverse microbial exposure. We find that wildlings develop stronger allergic inflammation in response to house dust mites with allergic T cell responses driven not only by cognate peptide antigens, but also by innate cytokines. In all, the results suggest that high microbial content and diversity potentiates, rather than restricts, allergic immune responses.

The Hygiene Hypothesis and New Perspectives—Current Challenges Meeting an Old Postulate

During its 30 years history, the Hygiene Hypothesis has shown itself to be adaptable whenever it has been challenged by new scientific developments and this is a still a continuously ongoing process. In this regard, the mini review aims to discuss some selected new developments in relation to their impact on further fine-tuning and expansion of the Hygiene Hypothesis. This will include the role of recently discovered classes of innate and adaptive immune cells that challenges the old Th1/Th2 paradigm, the applicability of the Hygiene Hypothesis to newly identified allergy/asthma phenotypes with diverse underlying pathomechanistic endotypes, and the increasing knowledge derived from epigenetic studies that leads to better understanding of mechanisms involved in the translation of environmental impacts on biological systems. Further, we discuss in brief the expansion of the Hygiene Hypothesis to other disease areas like psychiatric disorders and cancer and conclude that the continuously developing Hygiene Hypothesis may provide a more generalized explanation for health burden in highly industrialized countries also relation to global changes.