Effect of Nano Cerium Dioxide on Intestinal Microflora in Rats by Oral Subchronic Exposure

Abstract

Abstract Objective: To investigate intestinal toxicity in rats and effects on intestinal flora after oral subchronic exposure to nano cerium dioxide. Method: Forty healthy male SD rats were randomly divided into four groups: a control group (deionized water) and groups treated with different doses of nano ceria (e.g., 20 mg/kg, 100 mg/kg, and 500 mg/kg), with 10 rats in each group. The rats were given intragastric administrations (every other day) for 90 days. After the last intragastric administration, fresh fecal samples were collected by pressing the abdomen, and the animals were sacrificed. Jejunum, ileum and cecum tissues were retained for pathological analysis by Hematoxylin-eosin staining. The stool samples of rats were sequenced by the Illumina NovaSeq sequencing platform, and the sequencing results were further analyzed by QIIME2 software. Results: The histopathology results showed that compared with the control group, in the middle- and high-dose groups, epithelial tissue was shed, lamina propria glandular structures were damaged or disappeared, and large numbers of inflammatory cells were distributed in the mucosa. The intestinal flora results showed that there were no significant differences in the α-/β-diversities in each dose group compared with the control group (P>0.05). Compared to the control group, the intestinal pathogenic bacteria, Mucispirillum and Streptococcus, increased significantly after nanocerium dioxide ingestion, while Weissella decreased. The abundances of Akkermansia in all dose groups were higher than in the control group, but the abundances decreased with increasing exposure dose. MetagenomesSeq analysis showed that, compared with the control group, the abundances of S24-7, Lactobacillus and Clostridiales in all experimental groups significantly decreased. Conclusions: There was no significant difference in gut microbiota diversity after subchronic oral exposure to nanocerium dioxide,but there can affect the structure and abundance of intestinal microflora in rats, and long-term exposure to high doses (>100 mg/kg) causes enteritis