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Sex Hormones, the Microbiome, and Autoimmune Risk

microscopic illustration of bacteria, model of bacteria, realistic illustration of microbes, escherichia coli, klebsiella, salmonella, clostridium, pseudomonas, mycobacterium, shigella, legionella


The impact of the microbiome on the onset of autoimmune conditions is well established—especially in the connection between ankylosing spondylitis and Klebsiella infection.1 Research on other autoimmune conditions, the microbiome, and the effects of sex hormones is unfolding. For instance, children with type 1 diabetes are known to have dysbiosis when compared to healthy controls.2 This dysbiosis creates a pro-inflammatory state, and in animal models, modulating the microbiome can reduce type 1 diabetes risk.3-4

Strategies to introduce bacteria into high-risk individuals are being explored with fecal transplants in animal models. Transfer of the gut microbiota of adult male non-obese diabetic mice into young female mice led to “elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity.”3

In a mouse model of lupus, microbiome treatment improved symptoms in female mice and castrated mice but not in intact males,5 reinforcing the role of sex hormones in the link between the microbiome and autoimmunity. The impact of sex hormones on autoimmunity is not new; as far back as 1991,6 prevalence of autoimmune conditions was known to follow a woman’s menarche to menopause, increasing during the former and declining during the latter.7Since the microbiome affects sex hormone production, and vice versa, the role of estrogen and the microbiome in autoimmunity continues to be of interest.8-9 Tailoring treatments for each gender may have beneficial effects in a range of conditions, including IBS.10

If you or a loved one have an auto-immune disorder we can help determine the cause and offer solutions that do more than simply treat or suppress symptoms. We offer comprehensive labwork and stool testing to help determine the underlying contributors in your blood and gastrointestinal tract that are influencing your immune system.

References

  1. Schwimmbeck PL, Yu DT, Oldstone MB. Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter’s syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease. J Exp Med. 1987;166(1):173-181. doi:10.1084/jem.166.1.173.
  2. Murri M, Leiva I, Gomez-Zumaquero JM, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med. 2013;11:46. doi:10.1186/1741-7015-11-46.
  3. Markle JG, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339(6123):1084-1088. doi:10.1126/science.1233521.
  4. Bibbò S, Dore MP, Pes GM, Delitala G, Delitala AP. Is there a role for gut microbiota in type 1 diabetes pathogenesis? Ann Med. 2017 Feb;49(1):11-22. doi:10.1080/07853890.2016.1222449.
  5. Mu Q, Zhang H, Liao X, et al. Control of lupus nephritis by changes of gut microbiota. Microbiome. 2017;5(1):73. doi:10.1186/s40168-017-0300-8.
  6. Grossman CJ, Roselle GA, Mendenhall CL. Sex steroid regulation of autoimmunity. J Steroid Biochem Mol Biol. 1991;40(4-6):649-659.
  7. Gubbels Bupp MR. Sex, the aging immune system, and chronic disease. Cell Immunol. 2015;294(2):102-110. doi:10.1016/j.cellimm.2015.02.002.
  8. Khan D, Ansar Ahmed S. The immune system is a natural target for estrogen action: opposing effects of estrogen in two prototypical autoimmune diseases. Front Immunol. 2016;6:635. doi:10.3389/fimmu.2015.00635.
  9. Gomez A, Luckey D, Taneja V. The gut microbiome in autoimmunity: sex matters. Clin Immunol. 2015;159(2):154-162. doi:10.1016/j.clim.2015.04.016.
  10. Mulak A, Taché Y, Larauche M. Sex hormones in the modulation of irritable bowel syndrome. World J Gastroenterol. 2014;20(10):2433-2448. doi:10.3748/wjg.v20.i10.2433.