Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity
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Abstract
Mighty Male Microbes Both genetic and environmental factors contribute to an individual's susceptibility to autoimmune disease, but the specific environmental influences are not well characterized. Markle et al. (p. 1084 , published online 17 January; see the Perspective by Flak et al. ) explored how microbial factors, in particular the gut microbiota, influence susceptibility to type 1 diabetes in mice. In the non-obese diabetic (NOD) mouse model of type 1 diabetes, female mice are significantly more susceptible to disease than males; however, this difference was not apparent under germ-free conditions. Transfer of cecal contents from male NOD mice to female NOD mice prior to disease onset protected against pancreatic islet inflammation, autoantibody production, and the development of diabetes and was associated with increased testosterone in female mice. Blocking androgen receptor activity abrogated protection. Thus, the microbiota may be able to regulate sex hormones and influence an individual's susceptibility to autoimmunity.
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The record
- Venue
- Science
- Topic
- Diabetes and associated disorders
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Hospital for Sick ChildrenUniversity of Toronto
- Funders
- National Human Genome Research InstituteCanadian Institutes of Health Research
- Keywords
- NodAutoimmunityMicrobiomeBiologyNOD miceHormoneAndrogenImmunologyTestosterone (patch)Sex hormone-binding globulinAndrogen receptorAutoimmune diseaseGut floraDiabetes mellitusAutoantibodyEndocrinologyImmune systemGeneticsCancerAntibodyProstate cancer
- Has abstract in OpenAlex
- yes