The microbiome — the kilogram of microbes that each of us carries around — has been shown to be involved in everything from obesity and type 2 diabetes to behaviour and sexual preferences. The composition and effects of the microbiome are very active areas of research, producing results which have challenged the way we think about the evolution and interactions of organisms, including ourselves. In a paper recently published in the journal Science, researchers showed for the first time that the make up of the microbiome differs between the sexes, linking these differences to changes in hormone levels and disease resistance.
Autoimmune diseases, in which the immune system malfunctions and attacks the body’s own cells, tend to affect females more often than males. Dr. Jayne Danska and her colleagues investigated the basis of this difference by studying a strain of mice with high rates of type 1 diabetes, which is an autoimmune disease. Female mice are twice as likely to develop the disease as males, and the disease is also more common in animals living in clean conditions, in keeping with the hygiene hypothesis.
When the researchers raised mice which had no gut bacteria, they found that the difference in susceptibility between the males and females disappeared. The two sexes now developed autoimmune diabetes about as often as each other, at a rate in between that of normal males and females. The team used genome sequencing technology to take a census of the gut bacteria in normal male and female mice and found something startling. Young male and female mice had similar kinds of gut bacteria, but around puberty the microbiome of the two sexes began to diverge; by the time they were adults, females and males had distinct populations of bacteria living in their gut.
To figure out whether these differences were linked with resistance to autoimmune diseases, the team gave doses of bacteria from adult males to young female mice. As they grew up, these mice developed a new kind of microbiome, a community of gut bacteria that was different from that of both males and females. They also proved to be resistant to type 1 diabetes, with the incidence rate dropping from 85% in normal females to 25% in the treated females.
Steroid hormones like testosterone are often used to treat autoimmune diseases, and one reason for the lower susceptibility of males might be the fact that they have higher levels of testosterone. Earlier research had shown that castrated males were more likely to develop autoimmune diabetes and testosterone treatments could protect females, so the researchers also checked the levels of testosterone in the females after giving them bacteria from males. Not only did they find that these mice had higher levels of testosterone than normal females, but they also showed that the improved resistance depended on the increase in testosterone. When female mice were given a testosterone inhibitor along with the bacteria from male mice, the rate of diabetes returned to normal.
“It was completely unexpected to find that the sex of an animal determines aspects of their gut microbe composition, that these microbes affect sex hormone levels, and that the hormones in turn regulate an immune-mediated disease,” said Dr. Danska. It’s a pretty startling result which may impact how we think about a variety of autoimmune diseases in humans, from multiple sclerosis to rheumatoid arthritis. Like a lot of science, though, it generates nearly as many questions as it does answers, from the possible role of the micrbiome in pubescent development to how the gut bacteria actually regulate testosterone. It also clearly underlines the fact that our microbiome isn’t really “something we have” but is a part and parcel of who we are, helping defining each of us, both as an individual and an ecosystem.
Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U, von Bergen M, McCoy KD, Macpherson AJ, & Danska JS (2013). Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science (New York, N.Y.), 339 (6123), 1084-8 PMID: 23328391