Redox homeostasis is essential for intestinal and systemic health and is regulated by antioxidant defense systems and redox-sensitive signaling pathways such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NF-κB). Disturbances in this balance promote oxidative stress, chronic inflammation, and disease progression. Increasing evidence indicates that microbiota-derived metabolites act as key modulators of redox biology by shaping host gene expression through receptor-mediated signaling, metabolic regulation, and chromatin-associated mechanisms, including histone modifications, DNA methylation, and changes in chromatin accessibility. This review discusses how major classes of microbiota-derived and microbiota-modulated metabolites, including short-chain fatty acids (SCFAs), secondary bile acids, tryptophan-derived metabolites, polyphenol metabolites, hydrogen sulfide, and lipid mediators, influence redox-sensitive signaling and epigenetic regulation. We highlight their effects on intestinal barrier integrity and immune cell function, with particular emphasis on macrophage polarization and T-cell differentiation. Finally, we consider the emerging translational relevance of the microbiota–metabolite–epigenetic axis, while emphasizing that biomarker development and therapeutic applications require further mechanistic validation and clinical studies.

Cutaneous T cell lymphoma (CTCL) comprises a heterogeneous group of skin-homing T cell malignancies, with mycosis fungoides (MF) and Sézary Syndrome representing the most frequent and clinically relevant entities. Their clinical behavior differs substantially: MF often follows an indolent course over years, whereas Sézary Syndrome is a distinct clinicopathological entity that is typically characterized by erythroderma, a high burden of circulating malignant T cells and frequent lymph node involvement. Early-stage MF can often be controlled with skin-directed therapies, but advanced, relapsed or refractory CTCL remains therapeutically challenging. Established treatments are selected primarily according to disease stage, disease compartment and surface-target expression, whereas most pathway-directed, redox-modulating and apoptosis-sensitizing approaches remain investigational. Increasing evidence indicates that malignant T cells are maintained by an interconnected survival network rather than by a single dominant oncogenic pathway. This network includes constitutive inflammatory signaling, nuclear factor kappa B (NF-κB) activation, apoptosis resistance, altered redox homeostasis, mitochondrial and metabolic adaptation, rat sarcoma viral oncogene homolog (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK) signaling and epigenetic regulation. These mechanisms cooperate to promote malignant T cell survival, therapy resistance, and disease progression, but they also create opportunities for targeted therapeutic intervention. Particular emphasis is placed on redox-regulated cell death, nuclear factor kappa B (NF-κB)-dependent survival, B-cell lymphoma 2 (BCL-2) family proteins, RAS pathway alterations, epigenetic sensitization and mechanism-informed treatment strategies. Integrating clinicopathological staging with molecular profiling and functional vulnerability screens may support more rational combination therapies and improve patient stratification in CTCL.