Gut bacteria may help explain some of the cardiovascular and metabolic benefits associated with vegetable-rich diets, according to new research from Karolinska Institutet. The study suggests that intestinal microbes can use dietary nitrate and plant-derived iron to produce molecules that may influence blood vessels and organs beyond the gut.
Published in Cell, the research identifies a previously unrecognized pathway through which the gut microbiota can transform nutrients found in foods such as beetroot and leafy green vegetables. The resulting compounds, known as dinitrosyl iron complexes, or DNICs, were associated with beneficial metabolic and cardiovascular effects in experimental models.
How vegetables feed gut microbes
Nitrate occurs naturally in vegetables including spinach, rocket, lettuce and beetroot, while non-haem iron is found in foods such as beans, whole grains and green vegetables.
The researchers found that gut bacteria can use nitrate and non-haem iron in processes that lead to the formation of DNICs.
Once produced in the intestine, these compounds were detected beyond the gut, including in the liver and kidneys. This suggests that microbiota-derived DNICs can enter the circulation and reach other tissues, potentially allowing them to influence physiological processes elsewhere in the body.
Gut microbes are important for DNIC production
The researchers combined experiments in mice with bacterial cultures, cell studies and analyses involving human samples to investigate how DNICs are formed and distributed.
Using chemical analytical techniques, they detected the complexes in multiple tissues rather than only in the intestine.
A particularly important finding came from germ-free mice, which are raised without a normal gut microbiota. DNICs were not detected in these animals under the conditions examined, providing evidence that intestinal microorganisms play an essential role in their formation.
The findings therefore point to an interaction between diet and the microbiome: nutrients entering the intestine provide components that bacteria can transform into biologically active molecules.
Health effects emerged in animal models
The researchers next investigated whether increasing DNIC availability could influence cardiovascular and metabolic health in experimental models.
They increased DNIC levels either through dietary supplementation involving nitrate and iron or by administering synthetically produced DNICs.
Higher DNIC availability was associated with lower blood pressure and improved blood-vessel function. The researchers also observed improvements in glucose regulation and reductions in liver fat in the animal models studied.
These results suggest that DNICs may contribute to physiological pathways relevant to cardiovascular and metabolic health.
However, the findings do not establish that DNIC production is responsible for the health benefits of vegetable-rich diets in humans. Vegetables contain many nutrients and bioactive compounds, and their associations with health cannot be attributed to a single microbiome-derived molecule on the basis of these experiments.
A new piece of the diet–microbiome connection
The study provides a possible mechanism connecting dietary nitrate, non-haem iron, gut microorganisms and physiological effects elsewhere in the body.
This is particularly interesting because nitrate-rich vegetables such as leafy greens and beetroot have previously been associated with cardiovascular benefits, while plant-based dietary patterns are linked to better cardiometabolic health.
The new findings suggest that the microbiome could participate in some of these effects by transforming dietary components into DNICs.
But much of the evidence remains experimental. The study does not yet show how important this pathway is for cardiovascular or metabolic disease risk in humans or whether people who naturally produce more DNICs have better long-term health outcomes.
Individual differences in diet and gut microbiome composition could also influence how efficiently these compounds are produced.
What researchers want to investigate next
An important next step will be developing reliable methods for measuring DNICs in people, including their concentrations in blood and tissues.
Such measurements could allow researchers to examine whether DNIC levels are associated with particular diets, microbiome characteristics or cardiovascular and metabolic outcomes.
Future studies could also investigate whether dietary changes or alterations to the gut microbiota can reliably influence DNIC production in humans.
Eventually, understanding this pathway could help determine whether it has therapeutic or preventive applications. However, the current findings are not evidence that people should take nitrate, iron or DNIC supplements to prevent cardiovascular or metabolic disease.
The research was conducted with collaborators at University Medical Centre Hamburg-Eppendorf and Johannes Gutenberg University Medical Centre Mainz in Germany.
Funding came from organizations including the Swedish Research Council, Swedish Heart-Lung Foundation, Novo Nordisk Foundation and European Research Council. The authors reported no conflicts of interest.
Overall, the study identifies a previously unrecognized way in which diet and the gut microbiome may interact. By converting dietary nitrate and non-haem iron into DNICs, intestinal bacteria appear capable of generating compounds that reach other organs and influence cardiovascular and metabolic processes in experimental models.
Further human research will be needed to determine whether this pathway contributes meaningfully to the long-term health benefits associated with vegetable-rich diets.
