Effects of Silicon Dioxide Nanoparticles (SiO₂NPs) on Human Gut Microbiota Composition and Metabolism

Silicon dioxide nanoparticles (SiO₂NPs) are widely used as anti-caking agents (food additive E551). Their impact on the human gut microbiota is poorly understood. We evaluated the short-term effects of amorphous SiO₂NPs using a computer-controlled in vitro gastrointestinal digestion and batch culture fermentation model inoculated with fecal microbiota from a single healthy adult donor. Three doses were applied, low 3.15 mg, medium 63 mg and high 1,260 mg, corresponding to human-equivalent intakes of 0.09, 1.8 and 36 mg/kg body weight per day, spanning the reported mean dietary intake of E551 and an upper-bound exposure scenario; controls received deionized water. We monitored microbial community composition and metabolic activity by 16S rRNA sequencing, quantification of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), ammonium concentration, and antioxidant capacity (FRAP and DPPH) over 12 h. Over this window and at these doses, SiO₂NP treatment did not significantly alter α- or β-diversity, total SCFA or BCFA concentrations, ammonium, or FRAP/DPPH activity. However, taxonomic shifts were dose-dependent: low doses enriched Collinsella and depleted Flavonifractor, the medium dose enriched an Escherichia-Shigella amplicon sequence variant, and the high dose enriched Faecalibacterium and unclassified Clostridia while reducing Subdoligranulum, Faecalitalea and Flavonifractor (all false discovery rate < 0.05); an increase in Akkermansia at the high dose did not survive correction for multiple testing. Integrated multi-omics analysis (DIABLO) revealed that high-dose exposure weakened linkages between butyrate-producing Firmicutes and SCFAs and shifted the metabolic profile from butyrate toward propionate fermentation, accompanied by strengthened associations between proteolytic taxa, BCFAs and ammonium. These findings suggest that short-term exposure to SiO₂NPs induces subtle, concentration-dependent functional restructuring of the gut microbiota without overall diversity loss, although, as a single-donor in vitro study, the results are hypothesis-generating and require confirmation across multiple donors and longer exposures.