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

@article{Markle2013SexDI,
  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},
  journal={Science},
  year={2013},
  volume={339},
  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… Expand
Gender bias in autoimmunity is influenced by microbiota.
TLDR
Although protection of males did not correlate with blood androgen concentration, hormone-supported expansion of selected microbial lineages may work as a positive-feedback mechanism contributing to the sexual dimorphism of autoimmune diseases. Expand
Microbiome manipulation modifies sex-specific risk for autoimmunity
TLDR
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. Expand
Impact of Gut Microbiota on Gender Bias in Intestinal Pro-inflammatory Immune Phenotype and Systemic Autoimmune Progression in Lupus-prone SNF1 mice
TLDR
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. Expand
Gut microbiota differently contributes to intestinal immune phenotype and systemic autoimmune progression in female and male lupus-prone mice
TLDR
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. Expand
Gut microbiota differently contributes to intestinal immune phenotype and systemic autoimmune progression in female and male lupus-prone mice.
TLDR
Overall, 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 contribute to gender differences in the intestinal immune phenotype and systemic autoimmune progression. Expand
Dynamics of Gut Microbiota in Autoimmune Lupus
TLDR
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. Expand
The microbiome as a target for endocrine disruptors: Novel chemicals may disrupt androgen and microbiome-mediated autoimmunity
TLDR
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. Expand
Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice
TLDR
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. Expand
Immune recognition and response to the intestinal microbiome in type 1 diabetes.
TLDR
Recent evidence linking gut microbiome composition and function to pancreatic autoimmunity is examined, highlighting the requirement for longitudinal studies and mechanistic investigations in human subjects and rodent models to identify the basis for microbiome modulation of T1D and to identify biomarkers and therapeutics to improve delayed onset and prevention of the disease. Expand
The Role of Gut Microbiota and Environmental Factors in Type 1 Diabetes Pathogenesis
TLDR
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. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 75 REFERENCES
Sex-Specific Effect of Insulin-Dependent Diabetes 4 on Regulation of Diabetes Pathogenesis in the Nonobese Diabetic Mouse1
TLDR
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. Expand
Two genetic loci regulate T cell-dependent islet inflammation and drive autoimmune diabetes pathogenesis.
TLDR
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. Expand
Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy
TLDR
It is indicated that host-microbial interactions that impact host metabolism can occur and may be beneficial in pregnancy and when transferred to germ-free mice, T3 microbiota induced greater adiposity and insulin insensitivity compared to T1. Expand
The NOD mouse: a model of immune dysregulation.
TLDR
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. Expand
Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 Diabetes
TLDR
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. Expand
The Idd4 Locus Displays Sex-Specific Epistatic Effects on Type 1 Diabetes Susceptibility in Nonobese Diabetic Mice
TLDR
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. Expand
Androgen treatment prevents diabetes in nonobese diabetic mice
  • H. Fox
  • Medicine
  • The Journal of experimental medicine
  • 1992
TLDR
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. Expand
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
TLDR
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. Expand
Polygenic control of autoimmune diabetes in nonobese diabetic mice
TLDR
Evidence of linkage of ten distinct loci to diabetes or the pre–diabetic lesion, insulitis, indicative of a polygenic mode of inheritance is obtained and a new application of multiple polychotomous regression methods is assessed. Expand
Role of autoantibodies in type 1 diabetes.
TLDR
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. Expand
...
1
2
3
4
5
...