The Interaction between the Host Genome, Epigenome, and the Gut–Skin Axis Microbiome in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease that occurs in genetically predisposed individuals. It involves complex interactions among the host immune system, environmental factors (such as skin barrier dysfunction), and microbial dysbiosis. Genome-wide association studies (GWAS) have identified AD risk alleles; however, the associated environmental factors remain largely unknown. Recent evidence suggests that altered microbiota composition (dysbiosis) in the skin and gut may contribute to the pathogenesis of AD. Examples of environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, irritants, pollution, and microbial exposure. Studies have reported alterations in the gut microbiome structure in patients with AD compared to control subjects, characterized by increased abundance of Clostridium difficile and decreased abundance of short-chain fatty acid (SCFA)-producing bacteria such as Bifidobacterium. SCFAs play a critical role in maintaining host health, and reduced SCFA production may lead to intestinal inflammation in AD patients. The specific mechanisms through which dysbiotic bacteria and their metabolites interact with the host genome and epigenome to cause autoimmunity in AD are still unknown. By understanding the combination of environmental factors, such as gut microbiota, the genetic and epigenetic determinants that are associated with the development of autoantibodies may help unravel the pathophysiology of the disease. This review aims to elucidate the interactions between the immune system, susceptibility genes, epigenetic factors, and the gut microbiome in the development of AD.

Acid-treatedStaphylococcus aureusinduces acute silkworm hemolymph melanization

“…On the human skin, various bacteria, including C. acnes and S. aureus , produce short-chain fatty acids such as lactic acid [32]. Moreover, S. aureus and C. acnes produce lipases that produce free fatty acids from sebum [27], which can decrease the pH of the skin.…”

IL-17A inhibitors alleviate Psoriasis with concomitant restoration of intestinal/skin microbiota homeostasis and altered microbiota function

“…Multiple studies have demonstrated that dysbiosis of the gut microbiota, characterized by a reduction in SCFAs-producing bacteria, plays a pivotal role in the development of AD (81). For instance, Clostridium, Prevotella, Clostridia, Bifidobacteraceae, Bifidobacterium, Bacteroidetes, Christensenellaceae_R7_group, and other bacterial species have been found to be decreased (82)(83)(84)(85). Additionally, the "gut-skin" axis has emerged as a novel therapeutic target for the prevention and management of AD.…”

Gastrointestinal Comorbidities Associated with Atopic Dermatitis—A Narrative Review

“…It is a well-known fact that patients with AD present differences in terms of gut microbiota in comparison to healthy individuals, and this can also be a subject of study and an explanation for the higher prevalence of certain diseases in AD patients or the other way around [86]. According to the review conducted by Pessoa et al, patients with AD have a higher prevalence of Clostridium difficile and Staphylococcus aureus in comparison to healthy individuals, contrary to reduced colonization of Bifidobacteria and Bacteroides when compared to healthy controls [86]. Additionally, it is worth mentioning that recent research on the role of dysbiosis in the gut microbiota in the pathogenesis and course of AD has made progress.…”