2026-08-19 カロリンスカ研究所（KI）
＜関連情報＞
- https://news.ki.se/gut-bacteria-convert-dietary-nitrate-and-iron-into-protective-molecules
- https://www.cell.com/cell/fulltext/S0092-8674(26)00924-4
腸内細菌叢は、心血管代謝に有益なジニトロシル鉄錯体を生成する Gut microbiota generate dinitrosyl iron complexes with cardiometabolic benefits
Andrei L. Kleschyov ∙ Miho Shimari ∙ Ariela Maína Boeder ∙ … ∙ Eddie Weitzberg ∙ Jon O. Lundberg ∙ Mattias Carlström
Cell Published:August 19, 2026
DOI:https://doi.org/10.1016/j.cell.2026.07.055
Highlights
- Gut bacteria expressing nitrate reductase (NR) generate DNICs from nitrate and non-heme iron
- DNICs transfer to tissues and exert bioactivity via the Fe(NO)2 entity but not free NO
- DNICs alleviate experimental cardiometabolic disease and liver steatosis
- DNICs activate sGC, inhibit leucine uptake, and normalize aberrant mTORC1 signaling
Summary
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.
