Sodium fluoride induces hepatic and intestinal injury via gut microbiota dysbiosis and inflammatory activation: insights from network toxicology and 16S rRNA sequencing.

Fluoride is an essential trace element for human health. However, excessive intake of sodium fluoride (NaF) can induce fluorosis and lead to liver and intestinal injury. The mechanisms underlying NaF-induced hepatic and intestinal damage remain unclear. In this study, network toxicology was integrated with 16S rRNA high-throughput sequencing to elucidate the potential mechanisms of NaF toxicity, and the expression levels of key target proteins were further validated. Network toxicology analysis identified inflammatory mediators, including IL-6, IL-1β, and TNF-α, as central targets associated with NaF-induced hepatic and intestinal injury. In vivo experiments demonstrated dose-dependent accumulation of NaF in rat livers, accompanied by significant histopathological damage in both hepatic and intestinal tissues. Moreover, 16S rRNA sequencing revealed that NaF exposure increased the relative abundance of potentially pathogenic bacteria, including Firmicutes, Romboutsia, and Collinsella, while reducing the abundance of beneficial Bacteroides. Correlation analysis showed significant associations between altered gut microbiota composition and biochemical markers of liver and intestinal injury. These findings suggest that NaF-induced gut microbiota dysbiosis is closely linked to hepatic and intestinal damage, highlighting a potential mechanistic role of microbiota alterations in NaF-induced toxicity.