Lifestyle Changes and Industrialization in the Development of Allergic Diseases

Abstract

Purpose of review: Modernization and Westernization in industrialized and developing nations is associated with a substantial increase in chronic noncommunicable diseases. This transformation has far-reaching effects on lifestyles, impacting areas such as economics, politics, social life, and culture, all of which, in turn, have diverse influences on public health. Loss of contact with nature, alternations in the microbiota, processed food consumption, exposure to environmental pollutants including chemicals, increased stress and decreased physical activity jointly result in increases in the frequency of inflammatory disorders including allergies and many autoimmune and neuropsychiatric diseases. This review aims to investigate the relationship between Western lifestyle and inflammatory disorders.

Recent findings: Several hypotheses have been put forth trying to explain the observed increases in these diseases, such as 'Hygiene Hypothesis', 'Old Friends', and 'Biodiversity and Dysbiosis'. The recently introduced 'Epithelial Barrier Theory' incorporates these former hypotheses and suggests that toxic substances in cleaning agents, laundry and dishwasher detergents, shampoos, toothpastes, as well as microplastic, packaged food and air pollution damage the epithelium of our skin, lungs and gastrointestinal system. Epithelial barrier disruption leads to decreased biodiversity of the microbiome and the development of opportunistic pathogen colonization, which upon interaction with the immune system, initiates local and systemic inflammation. Gaining a deeper comprehension of the interplay between the environment, microbiome and the immune system provides the data to assist with legally regulating the usage of toxic substances, to enable nontoxic alternatives and to mitigate these environmental challenges essential for fostering a harmonious and healthy global environment.

Keywords: Allergy; Environment; Epithelial barriers; Microbiome; Toxicity.

Fig. 1

Differences between rural and urban lives: Westernization brings urbanization, which draw most individuals to live in cities instead or rural areas. These people consequently face air pollution, harmful chemicals, processed food and they have limited physical activity, all of which led to a loss in microbiome, predisposition to inflammatory conditions, and Th-2 biased immune responses. These mentioned factors collectively provide a tendency to epithelial barrier disruption, which underlies several inflammatory diseases including allergies, autoimmunity and neuropsychiatric conditions.

Fig. 2

Environmental contribution to allergic response: The agents which are collectively termed as epithelial barrier disruptors harm epithelial barrier integrity, followed by initiation of epithelitis and release of alarmins such as IL-25, IL-33 and TSLP, all of which trigger immune responses. Alarmins secreted by epithelial cells activate dendritic cells (DCs) and type-2 innate lymphoid cells (ILC2) to induce Th2-type immunity. Disruption of epithelial barriers initiates microbial translocation, which contributes to a chronic expulsion response, triggered by rich milieu of Th2-type cytokines, supported by eosinophils and mast cells, by the production of mediators such as LTs, MBP and histamine, LTC4, PGD2 and tryptase. Commensal bacteria invade inside and beneath the epithelium and elicits cell migration and initiation of immune responses. When an allergen is captured by DCs , it is processed and presented to naïve CD4⁺ T lymphocytes. With the presence of IL-4 in the milieu, naïve CD4⁺ T cells are polarized to Th2-type T cells which can produce IL-4, IL-5, IL-9, IL-13, and GM-CSF, collectively termed as Th2-type cytokines. With the presence of Th-2 type cytokines, B cells class-switch to and produce allergen-specific IgE, which binds to specific IgE receptors present on mast cells, basophils and eosinophils; the effector cells of allergy. On the other hand, rich Th2-type cytokines activate and potentiate basophils and eosinophils. This phase is termed as sensitization, and if the same type of allergen is encountered for a second time, it directly binds to IgE antibodies present on effector cells of allergy and which immediately degranulate to release mediators such as histamine and leukotrienes. Activated immune cells including macrophages, DCs, mast cells, T and B cells, and ILCs migrate to the area and initiate a type-2 expulsion response with Th2 cells, IgE-producing B cells, ILC2, IL-4, IL-5 and IL-13 against opportunistic pathogens, commensals, allergens as well as pollutants. The opportunistic pathogens include Staphylococcus aureus, Pneumococcus, Haemophilus and Moraxella. IL-4, IL-13, IFN-γ, TNF-α, and TRAIL take part in the chronic expulsion response, leading to further epithelial damage. The inflammatory response together with translocated microbiome and microbial dysbiosis lead to defects in epithelium repair, and mis-closure of the barrier, which instigate a vicious cycle of leaky barriers and chronic inflammatory responses as well as microbial dysbiosis. Westernized life has important contribution in this process with introduction of epithelial barrier disruptors such as detergents, toxic chemicals, food additives, and pollution. Various pollens could be introduced to the environment due to careless plantation, while pollination times are altered, and periods are sustained due to global warming. An urban lifestyle leads to altered and limited microbiome, which could underlie increased Th2-type responses in industrialized countries.(DC: Dendritic cell, Eos: Eosinophil, GM-CSF: granulocyte colony-stimulating factor, IL: interleukin, ILC: Innate lymphoid cell, LTs: leukotrienes, M∅: Macrophage, MBP: Major basic protein, MC: Mast cell, PGD: prostaglandin, TRAIL: TNF-related apoptosis inducing ligand, TSLP: Thymic stromal lymphopoietin).

Fig. 3

The vicious circle of chronic epithelial barrier dysfunction: Disruption of epithelial barriers are induced by exposome and damaging agents, which is facilitated by genetic defects in barrier-related molecules. Chronic inflammation in the peri-epithelial area leads to chronic, defective epithelial barrier healing and aggravates the damage. Epigenetics play role in defective barrier healing capacity which in turn leads to epithelial barrier damage and is termed as epithelitis. Then, loss of biodiversity and microbial dysbiosis end up with translocation of microbiota to inter- end sub-epithelial areas. An expulsion response is initiated, leading to chronic inflammation in peri-epithelial area. Defective epithelial barrier healing continues with epigenetic regulation