The Role of Microbiota in the Pathogenesis of Bullous Pemphigoid and Pemphigus Vulgaris: Evidence, Controversies, and Perspectives

Abstract

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) represent the most prevalent conditions among autoimmune bullous skin diseases, considered a major cause of severe morbidity and, in certain cases, mortality. The hallmark of the two diseases is the presence of autoantibodies directed against proteins located in the basement membrane of the skin, which determines the formation of blisters. In recent years, interest in the role of microbiota in relation to health-disease status has progressively increased. In particular, based on the gut-skin axis, accumulating evidence has emerged on the potential association between the composition and diversity of microbial communities in the gut, skin, and even in the oral cavity and the risk of developing BP and PV. Dysbiosis, characterized by a generally higher relative abundance of Firmicutes and a depletion of probiotics/beneficial species, might contribute to the pathogenesis of both diseases. Despite the still limited number of studies and the need for further large-scale multicenter studies, the knowledge gathered so far is suggestive of a novel modifiable risk factor representing a potential target for adjuvant treatments of these disabling and life-threatening conditions.

Keywords: autoimmune bullous skin diseases; bullous pemphigoid; gut microbiota; oral microbiota; pemphigus vulgaris; probiotics; skin microbiota.

Figure 1

Schematic representation of the complex relationship between intestinal epithelium cells, the immune system, and the gut microbiota. The effects of gut microorganisms on the intestinal epithelium (light blue) and on the innate and adaptive immune systems (pink) are expressed through the inhibition of histone deacetylase activity and the activation of G protein-coupled receptor signaling. The actions of intestinal epithelial cells and immune cells on the microbiota are shown in grey. Image partially generated using the Microsoft Bing Artificial Intelligence tool (see text for more details). Abbreviations: AMP: antimicrobial peptides; GPRC: G protein-coupled receptor; HDAC: histone deacetylase; IECs: intestinal epithelium cells; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells.

Figure 2

Summary of the biological effects produced by intestinal microbiota metabolites in a state of dysbiosis and potentially associated with the onset of inflammatory skin diseases (see text for more details). Vertical arrows indicate increased or decreased effector levels. Image partially generated using the Microsoft Bing Artificial Intelligence tool. Abbreviations: H₂S: hydrogen sulfide; SCFAs: short fatty acids; Th: T helper cell; TMAO: trimethylamine-N-oxide.