The epidermal lipid-microbiome loop and immunity: Important players in atopic dermatitis

Abstract

Background: The promotion of epidermal barrier dysfunction is attributed to abnormalities in the lipid-microbiome positive feedback loop which significantly influences the imbalance of the epithelial immune microenvironment (EIME) in atopic dermatitis (AD). This imbalance encompasses impaired lamellar membrane integrity, heightened exposure to epidermal pathogens, and the regulation of innate and adaptive immunity. The lipid-microbiome loop is substantially influenced by intense adaptive immunity which is triggered by abnormal loop activity and affects the loop's integrity through the induction of atypical lipid composition and responses to dysregulated epidermal microbes. Immune responses participate in lipid abnormalities within the EIME by downregulating barrier gene expression and are further cascade-amplified by microbial dysregulation which is instigated by barrier impairment.

Aim of review: This review examines the relationship between abnormal lipid composition, microbiome disturbances, and immune responses in AD while progressively substantiating the crosstalk mechanism among these factors. Based on this analysis, the "lipid-microbiome" positive feedback loop, regulated by immune responses, is proposed.

Key scientific concepts of review: The review delves into the impact of adaptive immune responses that regulate the EIME, driving AD, and investigates potential mechanisms by which lipid supplementation and probiotics may alleviate AD through the up-regulation of the epidermal barrier and modulation of immune signaling. This exploration offers support for targeting the EIME to attenuate AD.

Keywords: Adaptive immunity; Atopic dermatitis; Epidermal lipid; Lipid-microbiome loop; Microbe.

Graphical abstract

Fig. 1

Microbial disorders and abnormal lipid composition in AD. The development of AD involves adaptive immunity and an abnormal EIME, which is reflected in skin barrier dysfunction dominated by abnormal lipid composition and microbial disorders. In comparison to normal healthy skin, AD-lesioned skin exhibits a reduced proportion of CER EOS and LCFAs, and an increased variety and proportion of SCFAs and CERs. Moreover, the microbial balance can be disrupted by the colonization of opportunistic pathogenic bacteria. Abnormal EIME, in conjunction with adaptive immunity, drives AD. Figure created with Adobe Illustrator.

Fig. 2

A heat map illustrates the correlation between the microbiome (phylum and genus) and lipid profiles. The proportions of CER[NS] (A), SM (B), LPC(C), and ratios of LCFAs to SCFAs (D) in the skin of AD patients and healthy subjects. Spearman correlation coefficients between lipid profiles and skin microbiome are included . Copyright 2023, Kangmo Ahn and Donald Y.M. Leung.

Fig. 3

Abnormal states of microorganisms in EIME trigger adaptive immunity. These environmental abnormalities involve the abnormal proliferation of pathogenic bacteria (mainly S. aureus) that activate colonization resistance in the skin and trigger an immune response. Meanwhile, activated S. aureus secretes more virulence factors to intensify the immune response. The disordered microbiome alters the normal pH of the EIME and creates an alkaline pH environment that favors the proliferation of pathogenic bacteria, which activates the adaptive immunity. Figure created with Adobe Illustrator.

Fig. 4

The epidermal lipid-microbiome loop and the crucial role of immunity in AD. (A) Abnormalities within the lipid-microbiome positive feedback loop play a vital part in the imbalance of EIME in AD, encompassing the impairment of lamellar membrane integrity, increased susceptibility to epidermal pathogens, and modulation of both innate and adaptive immunity. (B) The relationship between epidermal lipid-microbiome loop and immunity in AD. Two kinds of immune-regulated barrier supplement measures, epidermal lipid compensates and complex microbial regulation, occur in EIME, which induces adaptive immunity. Activated adaptive immunity further consolidates abnormal lipid composition, strengthens epidermal pathogens colonization, and cascades amplifies AD inflammatory response. Figure created with Adobe Illustrator.