The effects of the oral administration of graphene oxide on the gut microbiota and ultrastructure of the colon of mice

Abstract

BACKGROUND: Graphene oxide (GO) has been widely used in the field of biomedicine and has shown great potential in drug delivery. Oral administration is an important mode of administration, but there are few studies on the effects of oral GO on gastrointestinal tract and gut microbiota. This study sought to explore the effects of oral GO on the gastrointestinal tract and gut microbiota. METHODS: In total, 20 C57BL/6 male mice, aged 5 weeks old, were randomly divided into the following 4 groups (n=5): the control group, the GO30 group, the GO60 group, and the GO120 group. The GO sample solution was administered intragastrically at the doses of 30, 60, or 120 mg/kg every 3 days, and the control group was given an equal volume of distilled water. On the 16th day, mouse feces were taken for 16S ribosomal ribonucleic acid (rRNA) sequencing analysis, and the mice were dissected, and the heart, liver, kidney, and colon removed for histological analysis. Additionally, the ultrastructure of the colon was observed by transmission electron microscopy. RESULTS: No obvious damage was observed in the hearts, livers, and kidneys of the mice. However, the intestinal ultrastructure of the mice in the GO group was damaged. The main manifestations were an uneven arrangement and local atrophy of the microvilli, swelling of the mitochondria and endoplasmic reticulum, and the widening of the intercellular spaces. The damage was positively correlated with increasing GO doses. The 16S rRNA sequencing results showed that the structure of the gut microbiota in the GO group was altered, and the contents of Alistipes, Enterobacteriaceae, Eubacterium, and Xanthobacteraceae were decreased. CONCLUSIONS: The oral administration of GO had no obvious toxicity effects on the hearts, livers, and kidneys of the mice. However, it did destroy the ultrastructure of the mouse colon and shift the structure of the gut microbiota, decreasing the contents of Alistipes, Enterobacteriaceae, Eubacterium, and Xanthobacteraceae.