Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity
Top Cited Papers
- 1 March 2013
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 339 (6123), 1084-1088
- https://doi.org/10.1126/science.1233521
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.Keywords
This publication has 52 references indexed in Scilit:
- Host Remodeling of the Gut Microbiome and Metabolic Changes during PregnancyCell, 2012
- Human gut microbiome viewed across age and geographyNature, 2012
- Investigating the biological and clinical significance of human dysbiosesTrends in Microbiology, 2011
- UCHIME improves sensitivity and speed of chimera detectionBioinformatics, 2011
- Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR ampliconsGenome Research, 2011
- Global patterns of 16S rRNA diversity at a depth of millions of sequences per sampleProceedings of the National Academy of Sciences of the United States of America, 2010
- Infernal 1.0: inference of RNA alignmentsBioinformatics, 2009
- Sex-specific genetic architecture of human diseaseNature Reviews Genetics, 2008
- SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARBNucleic Acids Research, 2007
- Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controlsNature, 2007