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by Helen Robertson

In 1933, identical twin baby boys Oskar Stohr and Jack Yufe were separated as a consequence of their parents’ divorce. Their subsequent upbringings could not have been more different: Oskar was brought up as a Catholic in Germany and became an enthusiastic member of the Hitler Youth. Jack remained in the Caribbean where they were born, was Jewish, and even lived for a time in Israel. Yet when they were reunited some fifty years after they last saw each other they had an uncanny number of similarities. They shared thought patterns, walking gait, a taste for spicy food, and perhaps most unusually, a habit of flushing the toilet before using it.

The unfortunate separation of identical twins provides scientists with an exceptional laboratory  for exploring the “nature vs nurture” conundrum. How much of our identity is conferred by our genes, and how much is a product of the environment in which we are raised? This is also true for our microbiome: twin studies have shown that the microbiomes of identical siblings are far more similar than those of fraternal twins, indicating that genes are at play.

UChicago researchers Alexander Chervonsky, PhD, and Tatyana Golovkina, PhD, are particularly interested in exploring how genetics—especially the genes that control our immune system— influence the composition of our microbiome. They chose to explore this question with mice.

Both mice and humans have two types of immunity: innate, “inborn” immunity, the first line of defense against pathogens, and adaptive immunity, in which immune cells are trained by the specific pathogens they encounter to fight off the same bad guys in the future.

To make sure all the mice used in the study started with the same microbes, Chervonsky and Golovkina needed to isolate them from the regular, bacteria-filled world. A normal mouse—much like a normal human—is born into an environment with trillions of bacteria, spread to them from their mothers and cagemates, their handlers, bedding, and food. Fortunately, UChicago’s special germ-free “gnotobiotic” mouse facility allows scientists to experiment on mice born and raised in an environment that hosts precisely zero bacteria, which make the mice experimental blank slates.

The researchers transferred microbes from a source mouse, raised in a conventional environment, to several strains of germ-free mice: some genetically identical, others with slight differences in their immune-response genes. In collaboration with computational immunologist Aly A Khan, PhD, they compared the resulting microbiomes to see if changes to immune system genes resulted in different types of microbial communities.

They found that differences in the adaptive—targeted—immunity caused minimal differences in microbial composition, and that those differences affected only certain strains of bacteria. Other types of bacteria even took advantage of the genetic differences and multiplied.

The team was surprised to discover that it was the innate immune response—the one the mice were born with, that needs no training: it was more active in shaping the microbiome. But even then, the total influence over the microbes in the mice’s gut was fairly small, meaning there were likely other genetic and non-genetic factors at play in determining how bacteria colonized and proliferated in the animals guts.

The team intends to look deeper into understanding how genes and microbes influence each other in developing animals. But this study sets a valuable benchmark for future microbiome work: closely documenting how the immune system worked here in germ-free mice means comparisons against other studies are standardized. Now we have a better idea of the “nature” side of the equation.

The Gnotobiotic Research Animal Facility is a vital asset for researchers at UChicago, and just one example of the gold standard approaches being used by the Duchossois Family Institute to improve our understanding of the underlying components of health and wellness.

Helen Robertson is a postdoctoral scholar in Molecular Evolutionary Biology at the University of Chicago, with a keen interest in science communication and science in society.