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0This research identifies a novel biological pathway where gut microbiota utilize dietary nitrate and non-heme iron to produce dinitrosyl iron complexes (DNICs). These bioactive molecules travel from the intestines to peripheral tissues as stable entities, functioning as hormone-like signaling agents that operate independently of free nitric oxide. Experiments reveal that DNICs provide significant cardiometabolic protection by activating the sGC-cGMP pathway and inhibiting leucine uptake, which effectively prevents the overactivation of the mTORC1-SREBP1 signaling axis. Consequently, treatment with these complexes or a combination of nitrate and iron salts alleviates hypertension, glucose intolerance, and liver steatosis in animal and human cell models. The study suggests that the health benefits traditionally linked to nitrate-rich vegetables may actually be driven by these microbe-generated metabolites. This discovery highlights the gut-organ axis as a critical regulator of metabolic health through the production of unique chemical messengers.
References:
Kleschyov A L, Shimari M, Boeder A M, et al. Gut microbiota generate dinitrosyl iron complexes with cardiometabolic benefits[J]. Cell, 2026.
