Understanding Asthma and Allergies by the Lens of Biodiversity and Epigenetic Changes

Abstract

Exposure to different organisms (bacteria, mold, virus, protozoan, helminths, among others) can induce epigenetic changes affecting the modulation of immune responses and consequently increasing the susceptibility to inflammatory diseases. Epigenomic regulatory features are highly affected during embryonic development and are responsible for the expression or repression of different genes associated with cell development and targeting/conducting immune responses. The well-known, "window of opportunity" that includes maternal and post-natal environmental exposures, which include maternal infections, microbiota, diet, drugs, and pollutant exposures are of fundamental importance to immune modulation and these events are almost always accompanied by epigenetic changes. Recently, it has been shown that these alterations could be involved in both risk and protection of allergic diseases through mechanisms, such as DNA methylation and histone modifications, which can enhance Th2 responses and maintain memory Th2 cells or decrease Treg cells differentiation. In addition, epigenetic changes may differ according to the microbial agent involved and may even influence different asthma or allergy phenotypes. In this review, we discuss how exposure to different organisms, including bacteria, viruses, and helminths can lead to epigenetic modulations and how this correlates with allergic diseases considering different genetic backgrounds of several ancestral populations.

Keywords: allergies; asthma; epigenetics; holobiont; microbiome.

Figure 1

Interaction between multiple environmental exposures and epigenetic changes: impact on immune-mediated diseases. Polluting agents, environmental exposure, diet, age, drugs, and especially exposure to organisms (species of bacteria, fungi, protozoan, and helminths) act as inducers of epigenetic changes. Among the epigenetic modifications are DNA methylation and histone modifications. Histone acetylation increases DNA access and facilitates the process of transcription, increasing gene expression. The addition of a methyl group in CpG islands prevents the binding of transcription factors and represses gene expression. The interaction between environmental exposures and epigenetic variations begins in the embryonic period and continues throughout life, being strongly dependent on the environmental experiences/challenges of everyone. Such alterations can be highly modifiable by instantaneous adaptation to the environment or generate inheritable epigenetic patterns and consequences to offspring. Epigenetic mechanisms influence cell differentiation and polarization of immune responses, these events modulate biological responses, and can interfere with the development of different immune-mediated diseases such as cancer, asthma, allergies, autoimmune diseases.