Researchers at Karolinska Institutet have found that gut microbes can transform nitrate and iron from food into molecules that may help protect against cardiovascular and metabolic disease. The findings, published in Cell, uncover a previously unknown way the gut microbiota may influence important functions throughout the body.
Nitrate is found naturally in many vegetables, especially beetroot and leafy greens such as spinach, rocket, and lettuce. Non-haem iron — the form of iron found in plant-based foods such as beans, whole grains and green vegetables — is also a common part of the diet.
The researchers found that gut bacteria can combine nitrate and non-haem iron from food to produce compounds known as dinitrosyl iron complexes (DNICs). After they are formed, these molecules can be absorbed into the body and carried to different organs, particularly the liver and kidneys.
Gut Microbes Are Essential for DNIC Formation
The study drew on experiments involving mice, cells, bacteria and human samples. Using advanced analytical techniques, the researchers detected DNIC in several types of tissue.
They also found that DNIC molecules were completely absent in germ-free mice. That result suggests that gut microbes play an essential role in producing them.
“Our results show that gut bacteria can convert components in food into biologically active molecules that influence important bodily functions,” says Andrei L. Kleschyov, Senior Researcher at the Department of Physiology and Pharmacology, Karolinska Institutet, the study’s first and co-corresponding author.
Higher DNIC Levels Improved Key Health Markers
The researchers then tested what happened when DNIC levels were increased. They did this either by giving dietary supplements containing nitrate and iron or by administering synthetically produced DNIC.
In an animal model of cardiovascular and metabolic disease, higher DNIC levels were associated with improvements in several measures of health.
“Among other things, we observed lower blood pressure and improved vascular function, better blood sugar control and reduced fat accumulation in the liver. The results help to explain why a diet rich in vegetables, which contain both nitrate and iron, is linked to a lower risk of several diseases,” says Mattias Carlström, Professor of Cardiorenal Physiology at the Department of Physiology and Pharmacology, Karolinska Institutet, one of the study’s shared last authors together with Professor Jon Lundberg at the same department, and co-corresponding author.
A Possible Link Between Vegetables and Disease Protection
According to the researchers, the results reveal a previously unknown mechanism through which diet and specific gut bacteria may work together to support health.
The findings could also help explain why diets rich in vegetables are associated with a lower risk of cardiovascular and metabolic diseases. However, the researchers caution that much of the work was carried out in experimental models, so additional research will be necessary to determine exactly how the process operates in humans.
Researchers Now Want to Study DNIC in Humans
The next goal is to develop reliable ways to measure DNIC levels in people. Researchers also want to learn more about how the molecules are produced, how they move through the body, and how they influence different physiological processes.
Another major question is whether diet or changes to the gut microbiota could be used to alter DNIC levels and potentially help prevent disease.
The study was carried out in collaboration with the University Medical Centre Hamburg-Eppendorf and the Johannes Gutenberg University Medical Centre Mainz in Germany. The research was funded by, amongst others, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the European Research Council (ERC), the Knut and Alice Wallenberg Foundation, Diabetes Wellness Sweden and the Karolinska Institute. The researchers state that they have no conflicts of interest.