## 5 Microbiome Influence on Atopic Dermatitis
### Dysbiosis in AD Patients  
The exact cause of AD is not completely understood; dysbiosis of the skin microbiota is believed to play a significant role in its development and exacerbation. Therefore, the molecular mechanisms of the underlying dysbiosis of the skin microbiota in atopic dermatitis will be briefly described [122]. Dysbiosis in AD is often associated with a decrease in microbial diversity on the skin, usually referred to as altered microbial diversity. The reduced diversity is thought to be driven by immune dysregulation in AD patients [123]. An overactive immune response can create an inhospitable environment for beneficial bacteria. AD is characterized by an abnormal immune response, including increased levels of pro-inflammatory cytokines such as interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-22 (IL-22) [124]. These cytokines contribute to skin inflammation and barrier dysfunction. In response to inflammation, the skin may produce antimicrobial peptides (AMPs) such as defensins and cathelicidins, which can disrupt the balance of skin bacteria [125]. These peptides are part of the skin's innate immune defense system, but can also harm beneficial bacteria. An altered lipid composition is also important to AD development. The skin's lipid barrier, composed of lipids such as ceramides, plays a critical role in maintaining the skin's integrity and preventing water loss. In AD, there is a disruption in the composition of these lipids that affects the growth and survival of certain skin microorganisms that metabolize specific lipid substrates, leading to imbalances in the skin microbiota [126]. _Staphylococcus aureus_ is often found in higher abundance on the skin of AD patients compared to healthy individuals. This bacterium can produce toxins and virulence factors that exacerbate skin inflammation. _Staphylococcus aureus_ can outcompete other commensal bacteria in AD patients, further reducing microbial diversity [15]. A compromised skin barrier, also called an impaired skin barrier, is a hallmark of AD. It allows for increased transepidermal water loss and the penetration of allergens, irritants, and microbes into the skin. The damaged skin barrier can create an environment that is conducive to the growth and colonization of pathogenic bacteria while hindering the growth of beneficial microbes [15]. Genetic factors also play a role in AD susceptibility. Mutations in genes related to skin barrier function and immune regulation, such as filaggrin (FLG) and various cytokine genes, can increase the risk of AD and contribute to dysbiosis [127].  
In summary, dysbiosis of the skin microbiota in atopic dermatitis is a complex interplay of altered microbial composition, immune dysregulation, changes in skin lipids, and impaired skin barrier function. These molecular mechanisms collectively contribute to the chronic inflammation and skin manifestations seen in AD. Understanding these mechanisms is crucial for developing targeted treatments to restore the balance of the skin microbiota and alleviate symptoms in AD patients.  
The mechanisms of the skin microbiota's influence on AD pathogenesis are depicted in Figure 2.