title: Microbiome manipulation modifies sex-specific risk for autoimmunity.
abstract: Despite growing evidence for a causal role of environmental factors in autoimmune diseases including the rise in disease frequencies over the past several decades we lack an understanding of how particular environmental exposures modify disease risk. In addition, many autoimmune diseases display sex-biased incidence, with females being disproportionately affected but the mechanisms underlying this sex bias remain elusive. Emerging evidence suggests that both host metabolism and immune function is crucially regulated by the intestinal microbiome. Recently, we showed that in the non-obese diabetic (NOD) mouse model of Type 1 Diabetes (T1D), the gut commensal microbial community strongly impacts the pronounced sex bias in T1D risk by controlling serum testosterone and metabolic phenotypes (1). Here we present new data in the NOD model that explores the correlations between microbial phylogeny, testosterone levels, and metabolic phenotypes, and discuss the future of microbiome-centered analysis and microbe-based therapeutic approaches in autoimmune diseases.
authors.affiliation: Department of Immunology; University of Toronto; Toronto, ON Canada; Program in Genetics and Genomic Biology; The Hospital for Sick Children; Toronto, ON Canada.
authors.forename: Janet G M
authors.initials: JG
authors.lastname: Markle
authors.affiliation: Division of Infectious Diseases; University of Colorado; Aurora, CO USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Frank
authors.affiliation: Department of Laboratory Medicine; The Hospital for Sick Children; Toronto, ON Canada; Department of Biochemistry; University of Toronto; Toronto, ON Canada.
authors.forename: Khosrow
authors.initials: K
authors.lastname: Adeli
authors.affiliation: Department of Metabolomics and Department of Proteomics; Helmholtz Center for Environmental Research; Leipzig, Germany; Department of Biotechnology, Chemistry, and Environmental Engineering; Aalborg University; Aalborg, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.affiliation: Department of Immunology; University of Toronto; Toronto, ON Canada; Program in Genetics and Genomic Biology; The Hospital for Sick Children; Toronto, ON Canada; Department of Medical Biophysics; University of Toronto; Toronto, ON Canada.
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Danska
mesh_terms: D000818:Animals; D015551:Autoimmunity; D058448:Biota; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D018570:Risk Assessment; D013739:Testosterone / Q000097:blood*
chemical_list: D013739:Testosterone
keywords: immune response to microbiome; metabolome; mouse models of autoimmunity; sex bias in disease; steroid hormones; type 1 diabetes