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

  title={Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity},
  author={Janet G. Markle and Daniel N. Frank and Steven Mortin-Toth and Charles E. Robertson and Leah M. Feazel and Ulrike E. Rolle-Kampczyk and Martin von Bergen and Kathy D. McCoy and Andrew J. Macpherson and Jayne S. Danska},
  pages={1084 - 1088}
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… 

Impacts of Gut Microbiota on Gender Bias in Intestinal Pro-Inflammatory Immune Phenotype and Systemic Autoimmune Progression in Lupus-prone SNF1 mice

It is shown that microbiota-dependent pro-inflammatory immune response in the gut mucosa of females initiated at juvenile ages and androgen-dependent modest protection of males contribute to gender differences in the intestinal immune phenotype and systemic autoimmune progression in lupus-prone SNF1 mice.

Microbiome manipulation modifies sex-specific risk for autoimmunity

New data in the NOD model is presented that explores the correlations between microbial phylogeny, testosterone levels, and metabolic phenotypes, and the future of microbiome-centered analysis and microbe-based therapeutic approaches in autoimmune diseases is discussed.

Gut microbiota differently contributes to intestinal immune phenotype and systemic autoimmune progression in female and male lupus-prone mice

This work shows that microbiota-dependent pro-inflammatory immune response in the gut mucosa of females initiated at juvenile ages and androgen-dependent protection of males contributes to gender differences in the intestinal immune phenotype and systemic autoimmune progression.

Dynamics of Gut Microbiota in Autoimmune Lupus

The dynamics of gut microbiota in murine lupus are demonstrated and evidence is provided to suggest the use of probiotic lactobacilli and retinoic acid as dietary supplements to relieve inflammatory flares in l upus patients.

The microbiome as a target for endocrine disruptors: Novel chemicals may disrupt androgen and microbiome-mediated autoimmunity

Transfer of microbiota from adult NOD male mice to pre-pubertal female mice protects against later incidence of sex-biased type 1 diabetes, suggesting that novel synthetic and/or plant-derived chemicals may affect sex- biased autoimmune diseases through disruption of protective signaling networks between the microbiome and its host.

Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice

Findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.

The Role of Gut Microbiota and Environmental Factors in Type 1 Diabetes Pathogenesis

Results indicate that higher levels of diversity along with the presence of beneficial microbes and the resulting microbial-produced metabolites can act as protectors against T1D onset, however, the specifics of the interplay between host and microbes are yet to be discovered.

Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice

Gut microbiome mediates the preventive effect of estrogen on metabolic endotoxemia and low-grade chronic inflammation, the underlying causes of MS and chronic diseases, and suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.

Sex-Specific Effect of Insulin-Dependent Diabetes 4 on Regulation of Diabetes Pathogenesis in the Nonobese Diabetic Mouse1

Genetic linkage analysis of (NOD × NOR) × NOD backcross mice shows that progression to severe islet inflammation after CY treatment was controlled by the Idd4 and Idd9 loci, which showed striking sex-specific behavior in CY-accelerated disease.

Two genetic loci regulate T cell-dependent islet inflammation and drive autoimmune diabetes pathogenesis.

Using the NOD model, an early step in diabetes pathogenesis is identified that behaves as a highly penetrant trait and NOD-derived alleles at both the Idd5 and Idd13 loci regulate a T lymphocyte-dependent progression from a benign to a destructive stage of insulitis.

The NOD mouse: a model of immune dysregulation.

In this review, many of the important features of disease development and progression in the NOD strain are summarized, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice.

Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 Diabetes

Detailed differences in metabolic potential indicate that autoimmune subjects have a functionally aberrant microbiome, and data suggest that a consortium of lactate- and butyrate-producing bacteria in a healthy gut induce a sufficient amount of mucin synthesis to maintain gut integrity.

The Idd4 Locus Displays Sex-Specific Epistatic Effects on Type 1 Diabetes Susceptibility in Nonobese Diabetic Mice

Data demonstrate sex-dependent interaction effects on type 1 diabetes susceptibility and provide a framework for functional analysis of Idd4.2 candidate genes, which contains 29 genes and displayed a sex-specific, epistatic interaction with I dd4.1.1 in NOR.

Androgen treatment prevents diabetes in nonobese diabetic mice

  • H. Fox
  • Medicine, Biology
    The Journal of experimental medicine
  • 1992
In this study, androgen therapy, begun after the onset of insulitis, was found to prevent islet destruction and diabetes without eliminating the islet inflammation in female NOD mice.

Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination

It is shown that the commensal gut flora—in the absence of pathogenic agents—is essential in triggering immune processes, leading to a relapsing–remitting autoimmune disease driven by myelin-specific CD4+ T cells.

Role of autoantibodies in type 1 diabetes.

Well characterized, high throughput autoantibody assays are the mainstays of prediction of type 1A diabetes, diagnosis of the immune mediated form of diabetes, and are important for the design of trials for the prevention of type 2A diabetes.