title: Gender bias in autoimmunity is influenced by microbiota.
abstract: Gender bias and the role of sex hormones in autoimmune diseases are well established. In specific pathogen-free nonobese diabetic (NOD) mice, females have 1.3-4.4 times higher incidence of type 1 diabetes (T1D). Germ-free (GF) mice lost the gender bias (female-to-male ratio 1.1-1.2). Gut microbiota differed in males and females, a trend reversed by male castration, confirming that androgens influence gut microbiota. Colonization of GF NOD mice with defined microbiota revealed that some, but not all, lineages overrepresented in male mice supported a gender bias in T1D. Although protection of males did not correlate with blood androgen concentration, hormone-supported expansion of selected microbial lineages may work as a positive-feedback mechanism contributing to the sexual dimorphism of autoimmune diseases. Gene-expression analysis suggested pathways involved in protection of males from T1D by microbiota. Our results favor a two-signal model of gender bias, in which hormones and microbes together trigger protective pathways.
authors: Committee on Microbiology, The University of Chicago, Chicago, IL 60637, USA.
authors: Leonid
authors: L
authors: Yurkovetskiy
authors: Michael
authors: M
authors: Burrows
authors: Aly A
authors: AA
authors: Khan
authors: Laura
authors: L
authors: Graham
authors: Pavel
authors: P
authors: Volchkov
authors: Lev
authors: L
authors: Becker
authors: Dionysios
authors: D
authors: Antonopoulos
authors: Yoshinori
authors: Y
authors: Umesaki
authors: Alexander V
authors: AV
authors: Chervonsky
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D002369:Castration; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D054892:Metagenome; D051379:Mice; D016688:Mice, Inbred NOD; D012727:Sex Characteristics
chemical_list: D000728:Androgens; D007371:Interferon-gamma
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