A recent report by Janet Markle et al., in Science magazine, identifies a possible causative link between gut microbiota and sex hormone production that may drive protection from autoimmunity.
The human gastrointestinal (GI) tract houses an extensive microbial ecosystem, represented by trillions of microorganisms located in our intestines. In fact, there are 10 times more intestinal microbial cells than cells in the human body. Recent research implicates disrupted intestinal equilibrium, termed gut dysbiosis, in the pathogenesis of autoimmune, allergic and metabolic diseases, and colorectal cancer (S. Prakashet al., Biologics: Targets and Therapy, 2011; 5: 71).
The sexual dimorphism in autoimmunity, wherein women, in general, are more frequently affected than men, is a well known phenomenon, but its mechanism remains poorly understood.
In the study by Markle and colleagues, the international team of researchers used the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D) to show that the strong >2:1 female-to-male NOD T1D sex bias and incidence is lost in germ-free (GF) conditions, in contrast to specific pathogen-free (SPF) conditions. Of note, no hygiene-dependent effects were detected in relation to 17β-estradiol, but the authors showed that commensal colonization regulated testosterone production and/or usage.
In a series of experiments the authors demonstrate that the transfer of gut microbiota from adult males to immature females resulted in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and T1D protection.
These findings, combined with previous research, as specified by the authors – specifically data of incomplete concordance in monozygotic twins and the recent rise in autoimmune disease incidence in developed countries may overall indicate a causal role of environmental factors in autoimmune disease.
This work seems to support the hygiene hypothesis of autoimmune diseases that may provide the missing immunoregulatory environmental factor that is needed to explain the recent increases in autoimmune disease.
The study also provides further evidence that testosterone is protective against autoimmunity.
After the hunt for genetic factors of the last decades, this study may represent the renaissance of interest towards hormonal and environmental factors that regulate autoimmune disease development and expression.
Source: Science, 2013, 339:1084-8.doi: 10.1126/science.1233521. Epub 2013 Jan 17.
Read more: PubMed