Microbial Ecology of Sulfur Mustard Toxicity: From Dysbiosis to Restoration

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, <i>Gordonibacter</i>, and Lachnospiraceae UCG010) while promoting a 302-fold expansion of inflammation-associated <i>Escherichia/Shigella</i>. 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 <i>Escherichia/Shigella</i> 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.