To figure out how such an immune change could cause obesity, they tested the biomes of the mice with and without the immune alteration. They found that healthy mice have plenty of bacteria from a genus called Clostridia, but few from Desulfovibrio, and that their guts let most fat pass right through. Those with an altered immune system had fewer Clostridia and more Desulfovibrio, and this microbial balance helped the gut absorb more fats from food. These mice gained more weight and exhibited signs of type 2 diabetes.
“Whether this applies in humans, we don't know,” Hooper says, “but this is a tantalizing clue.”
Mice are not humans, but their microbiomes are about as complex as our own. Reduced Clostridia and increased Desulfovibrio are seen in people with obesity and type 2 diabetes. Bacteria can reasonably be expected to function similarly in the guts of different species. But even if they don’t, this experiment is a demonstration of principle: The immune system helps control the composition of the gut microbiome.
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It does so by regularly mounting low-level immune responses to keep populations of bacteria in check. “The gut is under a constant state of inflammation, so to speak—constant immune stimulation from all the microbes,” says Stephens, pushing back on the common misconception that inflammation is always bad. The role of the immune system in the gut is to maintain balance. Changes to the body’s defenses, which can happen as a result of age or illness, can cause certain species to flourish at the expense of others.
This is the interesting part to Steven Lindemann, a researcher at Purdue University who was not involved in the Utah study. He studies the effects of foods on the gut microbiome. “Although we know that, on the balance, diet is the strongest contributor to gut microbiome composition,” he said, this study suggests that when immune control of the colon breaks down, growth can become unchecked and cause problems with metabolic regulation.
Lindemann says the fact that the immune system regulates the inhabitants of the small intestine is well established. He compares the bowel wall to a customs checkpoint: The goal is to weed out bad actors and illegal cargo, but allow legitimate trade to progress as rapidly as possible. In the case of the immune-altered mice, he says, “we have a colonic border patrol that is seemingly out to lunch, allowing bad actor Desulfovibrio to bloom.”
If similar microbial changes have comparable effects in humans, it could have far-reaching implications for our diets. The very ideas of “nutritional value” and “calorie content” of food seem to vary based on the microbial population of the person eating it and, potentially, her immune status. A person’s own microbes—and those contained in any given food—would have to be considered as another component of the already flimsy calories-in, calories-out equation. This would also compound the challenges already facing nutrition labels.