Gut Microbiota Remodeling after Fecal Microbiota Transplantation Is Associated with Reduced Inflammation and Cardiac Injury in Fluoride-Arsenic Co-Exposed Rats.

Groundwater co-contamination with arsenic and fluoride (AsF) has emerged as a widespread environmental and public health concern. Although the individual toxicities of arsenic and fluoride have been extensively studied, the mechanisms responsible for their combined cardiotoxic effects are still unclear. To address this gap, we first conducted an integrated network toxicology analysis to predict the potential molecular pathways involved in AsF-induced cardiotoxicity. The analysis identified inflammatory signaling, particularly the TLR4/NF-κB pathway, as a potential key mediator. Based on these findings, we established an animal model with fecal microbiota transplantation (FMT) intervention to investigate the interactive effects of AsF exposure and the microbiota-mediated molecular mechanisms involoved. The results clearly show that FMT in AsF-exposed rats is associated with improvements in cardiac parameters, reductions in LPS and cytokine levels, and significant changes in gut microbial composition. The TLR4/NF-κB pathway is implicated as a plausible mediating mechanism in this process. Concurrently, shifts in the abundance of Bacteroidetes were associated with changes in blood pressure. Collectively, these findings provide a new perspective for understanding the cardiotoxicity of environmental co-contaminants and offer experimental support for therapeutic strategies targeting the gut-heart axis.