Food doesn’t always affect the body in the form we eat it. Gut bacteria can change nutrients into entirely new compounds, and a new study suggests that may be one way plant-rich diets influence health.
Researchers found that certain gut bacteria can combine nitrate and non-heme iron, two nutrients found in foods such as leafy greens, beets, beans, whole grains and nuts, into compounds called dinitrosyl iron complexes, or DNICs.
In mice, increasing those compounds improved blood pressure, blood sugar control, body composition and fat buildup in the liver. But the study did not show that eating more nitrate- and iron-rich foods produces the same effects in people.
The research, published in Cell, used a mix of mouse, bacterial, cell and human-sample experiments to figure out where the compounds came from and what they might do.
One of the clearest clues came from mice raised without gut bacteria. Researchers found DNICs in the liver and kidneys of ordinary mice but not in germ-free mice. When mice were given nitrate and iron together, DNIC levels rose substantially, but only when gut bacteria were present.
Human gut bacteria appeared capable of doing something similar. Fecal samples from 10 healthy adults produced the compounds when researchers exposed them to nitrate and iron in the lab.
That does not mean the same thing has been shown to happen at meaningful levels after people eat a meal. The human samples were tested outside the body, so researchers still need to learn how much of these compounds people normally make and whether higher levels affect health.
The researchers then tested whether boosting DNIC levels could help mice with diet-related metabolic problems.
Some mice received nitrate plus iron, which encouraged their gut bacteria to make more DNICs. Others received a lab-made version of the compounds.
Both approaches improved several problems seen in the untreated mice. Blood pressure came down, blood vessel function improved and blood sugar control got better. The mice also had less body fat and more lean mass.
The liver findings stood out as well. Untreated mice developed substantial fat buildup in the liver, while mice with higher DNIC levels had much less.
Researchers also tested the compounds on small clusters of human liver cells grown in the lab. DNIC treatment reduced fat buildup there, too. That adds another clue, but lab-grown liver cells are still very different from a living person.
The bigger idea behind the study is fairly simple: nutrients may not act alone.
Gut bacteria can take something from food, chemically change it and create a new substance that then affects other parts of the body. In this case, nitrate and iron appear to be raw materials for compounds that may influence blood vessels, blood sugar and fat metabolism.
That could eventually help explain some of the health benefits linked with diets rich in vegetables, beans, nuts and whole grains.
But the study does not prove that DNICs are the reason those foods are associated with better health, nor does it show that people should take nitrate or iron supplements to try to make more of them.
The mouse experiments used concentrated forms of nitrate and iron, not ordinary servings of food. Researchers also produced much higher DNIC levels than were naturally present in untreated animals.
Another unanswered question is whether everyone makes these compounds to the same degree. Gut bacteria vary from person to person, and the researchers studied only one bacterial species in detail.
The health experiments also used male mice only. The researchers said female mice in this particular disease model did not develop the same clear metabolic problems, so whether the effects would be similar in females remains unknown.
The study was funded by the Swedish Research Council, Swedish Heart-Lung Foundation, Diabetes Wellness Sweden, Novo Nordisk Foundation, Ekhaga Foundation, German Research Foundation, European Research Council, Knut and Alice Wallenberg Foundation and Karolinska Institutet.