Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity

被引：1638

作者：

Markle, Janet G. M. ^{[1
,2
]}

Frank, Daniel N. ^{[3
]}

Mortin-Toth, Steven ^{[1
]}

Robertson, Charles E. ^{[4
]}

Feazel, Leah M. ^{[3
]}

Rolle-Kampczyk, Ulrike ^{[5
]}

von Bergen, Martin ^{[5
,6
,7
]}

McCoy, Kathy D. ^{[8
]}

Macpherson, Andrew J. ^{[8
]}

Danska, Jayne S. ^{[1
,2
,9
]}

机构：

[1] Hosp Sick Children, Res Inst, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada

[2] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

[3] Univ Colorado, Div Infect Dis, Sch Med, Aurora, CO 80045 USA

[4] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA

[5] Helmholtz Ctr Environm Res, Dept Metab, D-04318 Leipzig, Germany

[6] Helmholtz Ctr Environm Res, Dept Prote, D-04318 Leipzig, Germany

[7] Aalborg Univ, Dept Biotechnol Chem & Environm Engn, DK-9000 Aalborg, Denmark

[8] Univ Bern, Maurice Muller Labs, Univ Klin Viszerale Chirurg & Med, CH-3008 Bern, Switzerland

[9] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada

来源：

SCIENCE | 2013年 / 339卷 / 6123期

基金：

加拿大健康研究院;

关键词：

DIABETES SUSCEPTIBILITY; NOD MOUSE; ASSOCIATION; PREVENTION; COOPERATE; TRENDS; MICE;

D O I：

10.1126/science.1233521

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：1084 / 1088

页数：5

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