title: Genome-wide mapping of gene-microbiota interactions in susceptibility to autoimmune skin blistering.
abstract: 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.
authors.affiliation: 1] Max Planck Institute for Evolutionary Biology, August-Thienemann-Street 2, D-24306 Plön, Germany [2] Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Girish
authors.initials: G
authors.lastname: Srinivas
authors.forename: Steffen
authors.initials: S
authors.lastname: Möller
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Sven
authors.initials: S
authors.lastname: Künzel
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.forename: John F
authors.initials: JF
authors.lastname: Baines
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
mesh_terms: D000818:Animals; D044822:Biodiversity; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000235:genetics* / Q000382:microbiology*; D020022:Genetic Predisposition to Disease; D007114:Immunization; D051379:Mice; D064307:Microbiota / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D012867:Skin / Q000382:microbiology; D013045:Species Specificity
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