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

Department of Chemistry and Bioscience

Research output: Contribution to journal › Journal article › Research › peer-review

1434 Citations (Scopus)

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
Journal	Science
Volume	339
Issue number	6123
Pages (from-to)	1084-1088
Number of pages	5
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1233521
Publication status	Published - 1 Mar 2013

Keywords

Animals
Autoimmunity
Cecum
Diabetes Mellitus, Type 1
Female
Gonadal Steroid Hormones
Intestines
Male
Metagenome
Mice
Mice, Inbred NOD
Sex Characteristics

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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.",

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AU - Markle, Janet G M

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

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

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.

KW - Animals

KW - Autoimmunity

KW - Cecum

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Gonadal Steroid Hormones

KW - Intestines

KW - Male

KW - Metagenome

KW - Mice

KW - Mice, Inbred NOD

KW - Sex Characteristics

U2 - 10.1126/science.1233521

DO - 10.1126/science.1233521

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SN - 0036-8075

VL - 339

SP - 1084

EP - 1088

JO - Science

JF - Science

IS - 6123

ER -

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

Abstract

Keywords

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