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

Markle, J. G. M.; Frank, D. N.; Mortin-Toth, S.; Robertson, C. E.; Feazel, L. M.; Rolle-Kampczyk, U.; von Bergen, Melanie; McCoy, Kathleen; Macpherson, Andrew; Danska, J. S. (2013). Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity. Science, 339(6123), pp. 1084-1088. American Association for the Advancement of Science 10.1126/science.1233521

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

McCoy, Kathleen and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0036-8075

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

13 Jun 2014 10:09

Last Modified:

06 Nov 2015 09:57

Publisher DOI:

10.1126/science.1233521

BORIS DOI:

10.7892/boris.53044

URI:

https://boris.unibe.ch/id/eprint/53044

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