Genome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering

• Published in: Nature communications Vol. 4; no. 1; p. 2462
• Main Authors: Srinivas, Girish, Möller, Steffen, Wang, Jun, Künzel, Sven, Zillikens, Detlef, Baines, John F., Ibrahim, Saleh M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.09.2013; Nature Publishing Group; Nature Pub. Group
• Subjects: 631/250/248; 631/250/249/1313; 631/250/249/2510; 692/698/2741/2135; Animals; Biodiversity; Chromosome Mapping; Disease Models, Animal; Environmental risk; Epidermolysis Bullosa Acquisita - genetics; Epidermolysis Bullosa Acquisita - microbiology; Genetic Predisposition to Disease; Health risks; Humanities and Social Sciences; Immunization; Mice; Microbial activity; Microbiota - genetics; multidisciplinary; Quantitative Trait Loci - genetics; Risk factors; Science; Science (multidisciplinary); Skin - microbiology; Skin diseases; Species Specificity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms3462

Susceptibility to chronic inflammatory diseases is determined by immunogenetic and environmental risk factors. Resident microbial communities often differ between healthy and diseased states, but whether these differences are of primary aetiological importance or secondary to the altered inflammatory environment remains largely unknown. Here we provide evidence for host gene–microbiota interactions contributing to disease risk in a mouse model of epidermolysis bullosa acquisita, an autoantibody-induced inflammatory skin disease. Using an advanced intercross, we identify genetic loci contributing to skin microbiota variability, susceptibility to skin blistering and their overlap. Furthermore, by treating bacterial species abundances as covariates with disease we reveal a novel disease locus. The majority of the identified covariate taxa are characterized by reduced abundance being associated with increased disease risk, providing evidence of a primary role in protection from disease. Further characterization of these putative probiotic species or species assemblages offers promising potential for preventative and therapeutic treatment development. The pathogenesis of inflammatory disorders afflicting the skin is multifactorial. Srinivas et al . show that diversity of the skin microbiota is a critical factor determining the susceptibility to epidermolysis bullosa acquisita, a chronic mucocutaneous autoimmune skin blistering disease.