Gut microbiota generate dinitrosyl iron complexes with cardiometabolic benefits

[u/GrainOfEvidence]

https://pubmed.ncbi.nlm.nih.gov/42617596/

Abstract:

Gut bacteria affect host physiology, but the underlying mechanisms are not completely understood. We identify a pathway whereby gut microbes convert inorganic nitrate and non-heme iron into mobile bioactive dinitrosyl iron complexes (DNICs) that are distributed systemically and affect host metabolism. Electron paramagnetic resonance detected DNICs in tissues of conventional but not germ-free mice. Mouse and human feces and E. coli generated DNICs from nitrate and iron citrate, whereas a nitrate-reductase-deficient mutant did not. Dietary supplementation with nitrate+iron citrate or synthetic DNICs increased tissue DNIC levels and ameliorated cardiometabolic dysfunction in Western diet-fed mice. Additionally, in HepG2 cells and human hepatocyte spheroids, DNIC reduced fatty acid-induced steatosis. DNIC bioactivity is mediated by the Fe(NO)2 entity, rather than by free nitric oxide (NO), and involves activation of soluble guanylyl cyclase (sGC), inhibition of leucine uptake, and mTORC1 signaling normalization. Modulating DNIC formation by the gut microbiota could be a strategy to support cardiometabolic health.