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Crosstalk Between Microbiome and Ferroptosis in Diseases: From Mechanism to Therapy

Siqi Ding, Yun Lei, Zhe‐Ming Zhao, Xin‐Yun Li, Ji‐Xuan Lang, J.S. Zhang, Yanan Li, Chun‐Dong Zhang, Dong‐Qiu Dai

2025Comprehensive physiology8 citationsDOIOpen Access PDF

Abstract

The human microbiome is a unique organ and maintains host immunomodulation and nutrient metabolism. Structural and functional microbiome alterations are commonly known as dysbiosis, which is strongly associated with disease progression. Ferroptosis is a novel iron-dependent cell death mode characterized by intracellular iron accumulation, increased reactive oxygen species (ROS), and lipid peroxidation (LPO). Importantly, the complex crosstalk between the microbiome and ferroptosis in disease has attracted considerable research attention. The microbiome influences ferroptosis by regulating host iron homeostasis, mitochondrial metabolism, and LPO, among many other pathways. Thus, the in-depth analysis of microbiome-ferroptosis crosstalk and associated mechanisms could provide new strategies to treat human diseases. Therefore, understanding this crosstalk is critical. Here, we systematically explore the associations between gut microbiome and ferroptosis across multiple diseases. We show that the oral microbiome also influences disease progression by regulating ferroptosis. Furthermore, we provide a potential for certain disease therapies by targeting the crosstalk between the microbiome and ferroptosis.

Topics & Concepts

CrosstalkMicrobiomeDysbiosisBiologyDiseaseHuman microbiomeCell biologyBioinformaticsImmunologyMedicinePhysicsPathologyOpticsFerroptosis and cancer prognosisEpigenetics and DNA MethylationCancer, Lipids, and Metabolism
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