Gut bacteria found to unlock cardiometabolic benefits of dietary nitrate

Clinical takeaway: A newly identified pathway linking dietary nitrate, gut bacteria, and cardiometabolic function may help explain how the microbiome influences cardiovascular and metabolic health.

Cardiometabolic benefits linked to nitrate-rich foods such as beetroot, spinach, arugula, and lettuce have generally been attributed to the body's ability to convert dietary nitrate into nitric oxide, a molecule involved in regulating blood vessel function, blood pressure, and metabolism. New research suggests gut bacteria may play a more direct role than previously recognized, converting dietary nitrate and non-heme iron into bioactive compounds that influence cardiovascular and metabolic function.

The finding offers a new explanation for how foods associated with lower cardiovascular and metabolic risk may exert effects throughout the body. Instead of acting through dietary nitrate alone, some of those effects may depend on metabolites produced by gut microbes and transported to distant organs.

Researchers identified a microbiome-driven pathway that produces dinitrosyl iron complexes (DNICs), compounds formed when nitrate-reducing bacteria metabolize dietary nitrate and non-heme iron. DNICs were present in conventional mice but absent in germ-free mice, suggesting gut microbes are essential for their formation. Human fecal bacteria also generated DNICs when exposed to nitrate and iron in laboratory experiments.

“Our results show that gut bacteria can convert components in food into biologically active molecules that influence important bodily functions,” said Andrei L. Kleschyov, senior researcher at Karolinska Institutet.

The next question was whether those molecules produced meaningful physiologic effects. In a mouse model of cardiometabolic disease, liver DNIC levels were about 50% lower than in healthy controls. Raising DNIC levels through dietary nitrate plus iron or through synthetic DNIC treatment improved several markers of cardiometabolic health. Compared with untreated animals, treated mice had lower blood pressure, improved vascular function, better glucose control, and less liver steatosis. DNIC treatment also reduced fat accumulation in human liver spheroids exposed to free fatty acids.

Beyond helping digest food, gut bacteria appeared to generate compounds that influenced pathways involved in blood pressure regulation, glucose control, vascular function, and liver fat accumulation. The results suggest that at least some cardiometabolic effects associated with nitrate-rich foods may depend on the microbiome's ability to produce these molecules.

The broader significance extends beyond nitrate metabolism. By identifying bacteria-generated compounds that appear to influence multiple cardiometabolic pathways, the study offers a new framework for understanding how diet and gut microbes interact throughout the body. The discovery also strengthens the idea that the microbiome is not simply a modifier of nutrition, but an active contributor to cardiovascular, metabolic, and liver health.

Source: Kleschyov AL, et al. (2026 Aug 19) Cell. Gut microbiota generate dinitrosyl iron complexes with cardiometabolic benefits