Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases

International Inflammation (in-FLAME) Network of the World Universities Network (WUN). Electronic address: .
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 01/2013; 131(1):23-30. DOI: 10.1016/j.jaci.2012.11.019
Source: PubMed


The unparalleled burden of a diverse range of chronic noncommunicable diseases (NCDs) is a major global challenge in the 21st century. Chronic low-grade inflammation is a common feature of virtually all NCDs, indicating a central role of the immune system. Furthermore, as the most common and earliest-onset NCD, the epidemic of allergic diseases points to specific vulnerability of the developing immune system to modern environmental change. Indeed, many environmental risk factors implicated in the rise of other NCDs have been shown to mediate their effects through immune pathways. The innate immune system provides a clear example of this convergence, with evidence that physical activity, nutrition, pollutants, and the microbiome all influence systemic inflammation through Toll-like receptor pathways (notably Toll-like receptor 4), with downstream effects on the risk of insulin resistance, obesity, cardiovascular risk, immune diseases, and even mood and behavior. Common risk factors will likely mean common solutions, and interdisciplinary strategies to promote immune health should be an integral part of NCD prevention, with a greater focus early in the life course before disease processes are established. In this context allergic disease provides a very important early target to assess the effectiveness of environmental strategies to reduce immune dysregulation.

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Available from: Susan L Prescott, Jan 30, 2015
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    • "Animal models reveal that the gut microbiota directly interact with immune activity by changing the proportion of gut mRNA for chemokines, receptors, and FoxP3 (associated with regulatory T-cells) (150). More comprehensive reviews on the impact of human microbiota in early life are provided elsewhere (144, 151). To date, there has been limited research assessing the role of eukaryotes in microbial communities, further research of which are required to fully describe complex gut ecosystems in order to understand the role of the microbiome in health and disease. "
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    ABSTRACT: The concept of immunological memory stipulates that past exposures shape present immune function. These exposures include not only specific antigens impacting adaptive immune memory but also conserved pathogen or danger associated molecular patterns that mold innate immune responses for prolonged periods of time. It should thus not come as a surprise that there is a vast range of external or environmental factors that impact immunity. The importance of environmental factors modulating immunity is most readily recognized in early life, a period of rapidly changing environments. We here summarize available data on the role of environment shaping immune development and from it derive an overarching hypothesis relating the underlying molecular mechanisms and evolutionary principles involved.
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    • "The rapid increase in the prevalence of allergic diseases and other NCDs within a relatively short period can be attributed to environmental changes over the last few decades, as particular changes in dietary patterns, climate change, environmental pollution, and factors such as mode of delivery that shape microbial colonization patterns.6,8,9 These factors have been shown to promote the initiation and persistence of allergic and other inflammatory diseases through chronic low-grade inflammatory responses.10,11 "
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    ABSTRACT: During the last few decades, the prevalence of allergic disease has increased dramatically. The development of allergic diseases has been attributed to complex interactions between environmental factors and genetic factors. Of the many possible environmental factors, most research has focused on the most commonly encountered environmental factors, such as air pollution and environmental microbiota in combination with climate change. There is increasing evidence that such environmental factors play a critical role in the regulation of the immune response that is associated with allergic diseases, especially in genetically susceptible individuals. This review deals with not only these environmental factors and genetic factors but also their interactions in the development of allergic diseases. It will also emphasize the need for early interventions that can prevent the development of allergic diseases in susceptible populations and how these interventions can be identified.
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    • "Third, consistent with the fact that allergy is the most common and earliest-onset of inflammatory NCDs [87], it is important to understand how the immune mechanisms underlying food allergy interact with the ones constituting other NCDs, including other types of allergy, metabolic diseases, autoimmunity, and cancer. It is noteworthy to mention that there are common risk factors for most NCDs, that is, diet patterns, microbial patterns, behaviour, and environmental pollutants [87]. These common risks may initiate similar alterations within the immune system to cause many NCDs, arguably through the impairment of TReg cells. "
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    ABSTRACT: Food allergy is an aberrant immune-mediated reaction against harmless food substances, such as cow's milk proteins. Due to its very early introduction, cow's milk allergy is one of the earliest and most common food allergies. For this reason cow's milk allergy can be recognized as one of the first indications of an aberrant inflammatory response in early life. Classically, cow's milk allergy, as is true for most other allergies as well, is primarily associated with abnormal humoral immune responses, that is, elevation of specific immunoglobulin E levels. There is growing evidence indicating that cellular components of both innate and adaptive immunity play significant roles during the pathogenesis of cow's milk allergy. This is true for the initiation of the allergic phenotype (stimulation and skewing towards sensitization), development and outgrowth of the allergic disease. This review discusses findings pertaining to roles of cellular immunity in allergic inflammation, and tolerance induction against cow's milk proteins. In addition, a possible interaction between immune mechanisms underlying cow's milk allergy and other types of inflammation (infections and noncommunicable diseases) is discussed.
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