Gut Microbe Composition Varies Between Sexes.

When the gut microbiota of vertebrates is disturbed (technical term dysbiosis), it can cause a disruption in crucial digestive processes, potentially leading to obesity, diabetes, and inflammation.  Months ago, I wrote about a study that found gut microbes responsible for regulating weight gain, and there is a growing interest in manipulating the gut microbiota of humans to treat diseases arising from dysbiosis.  As it turns out, gut microbes also behave differently in males and females vertebrates, even when diets are identical.  This new finding may encourage sex-specific nutritional treatments to diseases and improve human health.

A three-spined stickleback

Sex is a genetic trait, and it influences gut microbiota through poorly understood mechanisms.  It has been proposed that there are hormone-microbe interactions, and that sex-specific immune responses play a role as well.  Using two species of fish, three-spined stickleback (Gasterosteus aculeatus), and European perch (Perca fluviatilis), the authors were able to measure within-population variations in diet, and compare gut microbiota between sexes.  They also completed in-depth analysis of data collected by other researchers working on different projects to show that this trend is consistent across disparate vertebrate species.

The authors characterized the gut microbiota from individuals of both fish populations by looking at the sequence of a specific region of bacterial 16S rRNA.  This is a very common method used in identifying the presence of different bacterial species in environmental samples.  There was a wide variation in the microbial composition within each population, but there was substantial conservation in composition across the two fish species - which is remarkable given that they diverged from each other ~50 million years ago, and they live across the globe from each other!  While both fish consume a similar diet, there is a lot of within-species variation in diet composition, which accounted for variation in gut microbial composition. 

This graph shows sex differences in sticklebacks fed
the same diet.  The blue line is males and the red
is females.  The circles represent fish fed insects, and the
triangles represent fish fed zooplankton.

But, what's most interesting in this study is that the variation in gut microbiota caused by diet variation was largely dependent on sex, and so diet effects in one sex cannot be used to predict diet effects in the other.  That means that, for example, studying the gut microbiota of a female stickleback who eats far more insect larvae than zooplankton won't tell you much about the gut microbiota of a male stickleback consuming the exact same diet (see figure, right).  In fact, comparison between stickleback females and perch females found more correlation between diet effects and gut microbiota than comparison of males and females within the same species.  Even though they are distinct species that live in completely different environments! 

To check if this same phenomenon was also true in other vertebrates, the authors compared the gut microbes of humans and mice.  They found the same trend in humans but not in mice.  Given that the fish and human studies were completed on individuals in their natural environments, while the mice were kept in a highly artificial lab environment, the authors are confident that their findings are real and can be extrapolated to other vertebrates.  They also warn that given the artificiality of the lab environment, much of the research done on lab mice may not be as informative as we think.

One of the more important aspects of this study is the contribution to the growing evidence that, medically, men and women need to receive different treatments.  Historically, medical research has avoided including female participants for a number of reasons, which has resulted in the gross misunderstanding of disease in women.  For example, men and women display very different heart attack symptoms, and yet many women dismiss their symptoms because they are not the "classic" symptoms we associate with heart attacks, often with devastating effects.  Hopefully with evidence like that presented in the study, sex differences will be taken into consideration when shaping treatment protocols for dysbiosis-related diseases.