Supersulfides, sulfur species containing catenated sulfur atoms, are potent reducing agents produced by diverse organisms. Although their intracellular functions are increasingly recognized, the ecological and physiological importance of gut microbial supersulfides remains poorly understood. In this study, we explored two complementary aspects of gut microbiota-derived supersulfide. First, by assessing the reducing activity, we found that bacterial supersulfides contribute to the enhancement of the extracellular reducing capacity. In particular, Dorea longicatena and Enterocloster bolteae exhibit strong cystine-dependent supersulfide production, which is associated with protection against oxidative stress. Second, beyond their ecological roles, supersulfides influence protein supersulfidation, which is a reversible post-translational modification. Supersulfidated proteins have been detected across multiple commensal taxa with species-specific profiles. This modification is redox-sensitive and modulated by extracellular supersulfides. Members of the Lactobacillaceae family are particularly susceptible to exogenous supersulfides. Supersulfidation involves proteins linked to core microbial processes, including bile acid metabolism, suggesting their potential role in tuning bacterial functions. Together, these findings suggest that microbial supersulfides act as dual regulators: (i) contributing to a protective reducing milieu and (ii) modulating bacterial protein function through supersulfidation. By highlighting post-translational control in gut bacteria and their sensitivity to the local redox environment, this work broadens the current models of microbial redox biology and provides a basis for linking bacterial sulfur metabolism with gut ecosystem stability and host-microbe interactions.

Heart failure is a major cause of mortality worldwide. Accumulating evidence indicates that mitochondrial dysfunction, particularly excessive generation of reactive oxygen species (ROS) from the mitochondrial electron transport chain (ETC), plays a vital role in the onset and progression of heart failure. Importantly, mitochondrial dysfunction is believed to emerge at an early stage of heart failure development. However, due to the lack of noninvasive techniques to directly evaluate cardiac mitochondrial function in vivo, the timing and dynamics of mitochondrial functional alterations during the early phase of heart failure development remain unclear. Carbamoyl-PROXYL (CmP) is a membrane-permeable nitroxyl probe that mediates redox reactions within the mitochondrial ETC in the presence of reduced nicotinamide adenine dinucleotide, thereby sensitively indicating mitochondrial electron transfer dynamics. We applied in vivo dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) to a mouse model of doxorubicin (DOX)-induced heart failure to validate its utility. In DOX-treated mice, the CmP reduction rate was significantly accelerated as early as 30 min after drug administration. However, no significant change was detected in epirubicin-treated mice compared with control animals. Considering that DOX induces ROS production through redox cycling at mitochondrial ETC complex I, these results demonstrate that in vivo DNP-MRI enables noninvasive visualization of ETC-associated mitochondrial redox imbalance in the living heart immediately after the onset of cardiotoxic stress, even when ROS generation has just begun and conventional functional changes are unapparent. Therefore, in vivo DNP-MRI represents a powerful noninvasive modality for the early diagnosis of heart failure.