When junk-food-loving microbes take over your intestines, they also change the architecture of your bone marrow, according to a recent study in Cell Metabolism.
When researchers at University of Erlangen-Nuremberg fed their lab mice a high-fat diet, they noticed inflammation in the bone marrow. And when the researchers transferred the gut bacteria from one of their obese mice to a skinny one, the skinny mouse’s marrow also began making immune cells in the same off-kilter pattern.
“That’s not a surprising thing,” said Dr. William Matsui, a bone marrow specialist at Johns Hopkins University School of Medicine who was not involved in the study. “You do anything that perturbs the animal, and it’ll do that. You go to the marrow and you see many, many more stem cells.”
Bone marrow—a diverse and active tissue—is home to a group of cells called the hematopoietic stem cells, which give rise to our body’s immune cells. Maintaining the proper number of immune cells is a balancing act; too many immune cells means throwing the entire system out of balance, but too few leaves us vulnerable to infection. Even small chemical signals can change the hematopoietic stem cells behavior.
“The thing that is not clear in our models and that we are trying to find now is how the microbiome is doing this work,” said Aline Bozec, the study’s senior author and a professor at the University of Erlangen-Nürnberg in Germany. “No bacteria can get to the bone marrow, so there is something secreted by the bacteria or the immune cells that goes back to the bone marrow.” As of now, Bozec’s team doesn’t know what that “secreted” something might be.
Bozec stressed that this study was preliminary and that even microbiome experts don’t know which bacterial species are causing the bone marrow to shift. Since gut bacteria secrete many different compounds, it is extremely difficult to sort out which are affecting different parts of the host’s anatomy.
For instance, Bozec and her team think the hematopoietic stem cells changed their behavior because, when the high-fat-diet bacteria arrived in the guts, they somehow caused the bone marrow to grow more fat cells. When the bone marrow grows more fat cells, those fat cells release compounds that cause the hematopoietic stem cells to make more of the inflammatory immune cells.
However, the researchers still don’t know which microbial species are behind the bone marrow changes. We do know that, in both mice and humans, junk food diets allow a slightly different set of bacteria to thrive than with low-fat diets. This study argues that the bacterial communities that live in obese mice could be driving fat cell growth in the bone marrow, but the sheer number of different bacterial combinations makes designing experiments that test their effects notoriously difficult.
Still, uncovering the role of the microbiome could open a new window to understanding diseases and developing new treatments. “It really is a part of our physiology,” said Nichole Broderick, a University of Connecticut microbiome researcher who was not involved with this study. “It’s not just a local effect; it’s having a systemic effect on multiple organs,” she added.
Bozec did note that when they gave the high-fat diet mice a drug that made the fat cells stop growing, the hematopoietic stem cells started behaving more like their counterparts in skinny mice. A better understanding of that pathway could lead to new treatments eventually.
“What we want to do is break the link between obesity and disease,” said Carey Lumeng, a University of Michigan pediatrician who studies high-fat diets’ effects on bone marrow but was not involved in this study. “This is one possible place to break the link, by halting the bone marrow inflammation.”