Distinct Fecal Microbiota and Serum Metabolite Profiles in Male Rat Exposed to Aluminum Oxide and Aluminum Oxide Nanoparticles

Abstract

The widely application of aluminum oxide nanoparticles (Al2O3 NPs) in industry and personal care products has been raising concerns about their potential adverse consequences. However, the knowledge on their influence on gut microbiota and serum metabolism remains poorly understood. This study employed an integrated approach combining 16S rRNA gene sequencing and untargeted metabolomics profiling to investigate the impact of a 28 days oral exposure to α- and γ-Al2O3 NPs and the equivalent dose of bulk Al2O3 on the toxic response, fecal microbiota composition and serum metabolites of male rats. At the equal dose of 100 mg/kg bw, α-Al2O3 NPs had a greater effect on white blood cell count, percent of monocytes, liver SOD activity and plasma GSH content, than that of γ-Al2O3 NPs and bulk Al2O3. 16S results revealed NPs exposure significantly perturbed the fecal microbiome composition, and the relative abundance of genus such as Desulfovibrio, Steroidobacter and Acidibacter was significantly reduced. A significantly lower alpha diversity and distinct microbial communities, as reflected by beta diversity, were observed in α-Al2O3 NPs treatment, compared to bulk Al2O3 and control. UHPLC-QTOFMS indicated that the circulating serum metabolites (e.g. 3-hydroxyisovaleric acid, dopamine, D-glucuronate) were significantly more abundant with α-Al2O3 NPs, while metabolites (e.g. corticosterone, glycerol, glycerol 3-phosphate) were significantly induced by γ-Al2O3 NPs. Pathway analysis further indicated potential defects in the D-glutamine and D-glutamate metabolism and phenylalanine, tyrosine and tryptophan biosynthesis in α-Al2O3 NPs, while glycerolipid and linoleic acid metabolism were significantly affected by γ-Al2O3 NPs. This study provides novel insights regarding the differential fecal microbiome and serum metabolome affected by nanoparticulate forms versus bulk forms of aluminum oxide in organisms.