The trillions of bacteria living inside the human digestive system do much more than help break down food.
They operate almost like a tiny chemical factory, transforming ingredients from our meals into substances that can travel through the body.
Scientists at Karolinska Institutet have now discovered a previously unknown example of this process. Certain gut bacteria appear able to use nutrients from vegetables to make compounds that could help protect against high blood pressure and metabolic disease.
The research was published in Cell. It was carried out with collaborators at the University Medical Centre Hamburg-Eppendorf and Johannes Gutenberg University Medical Centre Mainz in Germany.
Researchers focused on two substances that commonly occur together in plant-based diets: nitrate and nonheme iron. Both have familiar nutritional roles, but the new study suggests their interaction with gut bacteria may produce additional benefits.
Nitrate is especially abundant in leafy vegetables and beetroot. Although the word nitrate is sometimes associated with processed meats, naturally occurring nitrate from vegetables is consumed alongside many other beneficial nutrients and has been studied for its possible effects on blood vessels and blood pressure.
Nonheme iron is the main type of iron found in plants. Beans, lentils, whole grains and green vegetables are among its common dietary sources.
The scientists found that microbes in the intestine can use nitrate and iron to create unusual molecules known as dinitrosyl iron complexes, shortened to DNICs. Once formed, these molecules can leave the gut and enter the circulation.
The team detected them in different organs, with particularly noticeable levels in the liver and kidneys. This raised an important question: were the gut bacteria actually responsible for producing them?
To find out, researchers studied mice that had been raised without microorganisms in their digestive systems. DNICs were completely absent from these germ-free animals.
The result provided strong evidence that intestinal microbes are necessary for this particular pathway. In effect, nutrients entering the digestive system were being turned into something new through the combined activity of food and bacteria.
Scientists then explored whether these newly created compounds might affect health. They increased DNIC levels in animals showing features of cardiovascular and metabolic disease.
One approach involved giving nitrate and iron through the diet. Another involved providing laboratory-made DNICs directly.
The results were encouraging. Higher DNIC levels were associated with lower blood pressure and better functioning of the blood vessels.
The animals also controlled blood sugar more effectively. They accumulated less fat in their livers, another potentially valuable effect because fatty liver commonly occurs alongside obesity, insulin resistance and type 2 diabetes.
These findings may help connect two areas of research that have attracted enormous scientific interest: vegetable-rich diets and the gut microbiome. Large population studies have repeatedly linked diets containing plenty of vegetables with lower rates of cardiovascular disease and other chronic illnesses.
Usually, scientists look at nutrients such as fiber, potassium, vitamins and plant chemicals when trying to explain those benefits. The new study suggests another possibility: some benefits may depend on what gut bacteria do with the food after it reaches the intestine.
That idea could eventually help explain why two people eating similar foods do not always experience identical effects. Every person’s gut microbiome is somewhat different, and those differences can affect how food components are processed.
There are still major gaps in the evidence, however. The researchers used human samples as part of the investigation, but the disease-related benefits were mainly demonstrated in experimental models.
It is therefore too early to conclude that increasing DNIC levels will prevent high blood pressure, diabetes or fatty liver disease in people. The findings also do not establish that people should take nitrate or iron supplements, since unnecessary supplementation can carry risks and does not necessarily reproduce what happens when nutrients come from whole foods.
The researchers now plan to develop methods that can accurately measure DNICs in people. They want to understand how the compounds move through the human body, which gut bacteria make them and whether changing diet or the microbiome can reliably alter their levels.
Overall, the study is compelling because it identifies a specific chain of events linking diet, gut microbes and biological effects throughout the body. The disappearance of DNICs in germ-free mice provides particularly strong evidence that bacteria are essential to their production.
The health implications remain preliminary until larger human studies are completed. But if the pathway operates similarly in people, it could reveal another fascinating reason why eating plenty of vegetables benefits far more than the digestive system.
Source: Karolinska Institutet.
