The impact of metallic nanoparticles on gut fermentation processes: An integrated metabolomics and metagenomics approach following an in vitro digestion and fecal fermentation model

Metallic nanoparticles (MNPs) are becoming widespread environmental contaminants. They are currently added to several food preparations and cause a fast-growing concern for human health. The present work aims to assess the impact of zinc oxide (ZnO), titanium dioxide (TiO2), and silver (Ag) nanoparticles (NPs) on the human gut metabolome and microbiome. Water samples spiked with two different concentrations of each MNPs were subjected to in-vitro gastrointestinal digestion and in-vitro large intestine fermentation. The effects of the treatments were determined through 16 S amplicon sequencing and untargeted metabolomics. Multi-omics data integration was then applied to correlate the two datasets. MNPs treatments modulated the microbial genera Bifidobacterium, Sutterella, Escherichia and Bacteroides. The treatments, especially the lower concentrations of Ag and ZnO, caused modulation of indole derivatives, peptides, and metabolites related to protein metabolism in the large intestine. Notably, these metabolites are implicated in ulcerative colitis and inflammatory bowel disease. TiO2 NPs treatment in all concentrations increased E.coli relative abundance and decreased the abundance of B. longum. Moreover, for TiO2, an enrichment in proinflammatory lipid mediators of arachidonic acid metabo-lites, such as prostaglandin E2 and leukotrienes B4, was detected. For all metals except TiO2, low NP concen-trations promoted differentiated profiles, thus suggesting that MNPs aggregation can limit adverse effects on living cells.