Sulfur mustard (SM) is a blister‐producing chemical warfare agent which could lead to a cascade of systemic damage, especially severe acute lung injury. Oxidative stress is considered to be vital processes for the SM toxicity mechanism. We previously proved the therapeutic effect of exosomes derived from bone marrow mesenchymal stromal cells in promoting the repair of alveolar epithelial barrier and inhibiting apoptosis. However, the key functional components in exosomes and the underlying mechanisms have not been fully elaborated. This research shed light on the function of the key components of human umbilical cord mesenchymal stem cell‐derived exosomes (HMSCs‐Ex). We noted that HMSCs‐Ex‐derived miR‐199a‐5p played a vital role in reducing pneumonocyte oxidative stress and apoptosis by reducing reactive oxygen species, lipid peroxidation products and increasing the activities of antioxidant enzymes in BEAS‐2B cells and mouse models after exposure to SM for 24 h. Furthermore, we demonstrated that the overexpression of miR‐199a‐5p in HMSCs‐Ex treatment induced a further decrease of Caveolin1 and the activation of the mRNA and protein level of NRF2, HO1 and NQO1, compared with HMSCs‐Ex administration. In summary, miR‐199a‐5p was one of the key molecules in HMSCs‐Ex that attenuated SM‐associated oxidative stress via regulating CAV1/NRF2 signalling pathway.

Sulfur mustard (SM) causes multi-organ toxicity, yet its impact on intestinal tissue and the associated gut microbiota remains poorly characterized. This study demonstrates that in a mouse model of SM exposure, gut microbial ecological collapse occurs, characterized by depletion of protective taxa (Bifidobacteriales, Gordonibacter, and Lachnospiraceae UCG010) while promoting a 302-fold expansion of inflammation-associated Escherichia/Shigella. Mendelian randomization analysis established causal relationships between these SM-perturbed taxa and human inflammatory bowel disease. Fecal microbiota transplantation effectively restored microbial diversity (Simpson index: 0.85 to 0.95), suppressed Escherichia/Shigella by 97.4%, and ameliorated intestinal pathology. Longitudinal tracking revealed persistent vulnerability of Bifidobacteriales compared to other depleted taxa. Our findings establish the gut microbiota as a key mediator in SM intestinal toxicity and provide new insights for microbiota-targeted interventions against chemical injuries.

Sulfur mustard (SM), a persistent environmental contaminant in conflict zones, induces severe pulmonary and systemic toxicity through airborne, soil, and groundwater exposure routes. While the mechanisms and core targets of SM remain complex, computational network toxicology predicted six core targets (PTGS2, ESR1, APP, SIRT1, ACE, CASP3) converging on environmental stress responses, neurotoxicity cascades, and metabolic dysregulation. These alterations drive immunotoxicity, inflammatory responses, cytogenetic mutations, and ultimately leading to lung injury. Critically, RNA-seq validation confirmed CASP3 elevation (1.4-fold) and SIRT1 suppression (1.5-fold) as exposure biomarkers directly informing remediation policies for contaminated ecosystems. This integrated computational-experimental approach reveals novel therapeutic strategies against SM's public health impact.