Identification of the exposure pathway to micro-scaled biogenic silica debris via diet and its potential effect in promoting esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) has remained highly prevalent for decades in certain regions, such as the Taihang Mountains in China, though its etiology remains unclear. The previous study unveiled silica fragments in resected ESCC tissues in this region, raising a hypothesis about their relationship with ESCC. Yet, the exposure pathway of these silica fragments and their role in the high incidence of ESCC remain unclear. Here, we report micro-scaled needle-like biogenic silica debris (NL-BSDs) as contaminants in wheat flour, primarily originating from densest siliceous outgrowths on the lemma and palea of wheat husks. Simulating flour processing suggests that ineffective kernel-washing under water scarcity, a common climate feature for ESCC high-risk regions, allows more NL-BSDs to contaminate the flour. In addition, in an animal model, dietary exposure to NL-BSDs-bearing wheat husk potentially promotes tumorigenesis and induces inflammatory changes within esophagus and dysbiosis of gut microbiota, aligning with the classical two-stage tumorigenesis-initiation followed by promotion, suggesting that NL-BSDs contamination in diet could acts as a tumor promoter thus contributing to the high incidence of ESCC. Overall, our results suggest a previously neglected contamination in wheat flour and provide evidence for its potential adverse effects associated with esophageal tumors.