Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity

Janet G.M. Markle; Daniel N. Frank; Steven Mortin-Toth; Charles E. Robertson; Leah M. Feazel; Ulrike Rolle-Kampczyk; Martin Von Bergen; Kathy D. McCoy; Andrew J. Macpherson; Jayne S. Danska

doi:10.1126/science.1233521

Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity

Janet G.M. Markle, Daniel N. Frank, Steven Mortin-Toth, Charles E. Robertson, Leah M. Feazel, Ulrike Rolle-Kampczyk, Martin Von Bergen, Kathy D. McCoy, Andrew J. Macpherson, Jayne S. Danska

Research output: Contribution to journal › Article › peer-review

975 Scopus citations

Abstract

Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. We demonstrate that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.

Original language	English (US)
Pages (from-to)	1084-1088
Number of pages	5
Journal	Science
Volume	339
Issue number	6123
DOIs	https://doi.org/10.1126/science.1233521
State	Published - Mar 1 2013
Externally published	Yes

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title = "Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity",

abstract = "Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. We demonstrate that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.",

author = "Markle, {Janet G.M.} and Frank, {Daniel N.} and Steven Mortin-Toth and Robertson, {Charles E.} and Feazel, {Leah M.} and Ulrike Rolle-Kampczyk and {Von Bergen}, Martin and McCoy, {Kathy D.} and Macpherson, {Andrew J.} and Danska, {Jayne S.}",

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AU - Frank, Daniel N.

AU - Mortin-Toth, Steven

AU - Robertson, Charles E.

AU - Feazel, Leah M.

AU - Rolle-Kampczyk, Ulrike

AU - Von Bergen, Martin

AU - McCoy, Kathy D.

AU - Macpherson, Andrew J.

AU - Danska, Jayne S.

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AB - Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. We demonstrate that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.

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Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity

Abstract

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