Department of Basic Medicine and Forensic Medicine, Baotou Medical School, Inner Mongolia University of Science and Technology, Baotou, China.
Clinical Laboratory, the Second Affiliated Hospital of Baotou Medical College, Baotou, China.
PLoS One. 2024 Feb 29;19(2):e0298917. doi: 10.1371/journal.pone.0298917. eCollection 2024.
To investigate intestinal toxicity in rats and the effects of Nano-cerium dioxide on intestinal flora in rats after oral sub-chronic exposure.
Forty healthy male SD rats were randomly divided into four groups: a control group (deionized water) and three 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.
The histopathology results show 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 show that there were no significant differences in the α-/β-diversities in each Nano-ceria-treated group compared with the control group (P>0.05). Compared with the control group, the intestinal pathogenic bacteria, Mucispirillum and Streptococcus increased significantly after Nano-cerium dioxide ingestion, while Weissella decreased. The abundances of Akkermansia in all Nano-ceria-treated groups were higher than those in the control group, but the abundances decreased with increasing dose. MetagenomesSeq analysis show that, compared with the control group, the abundances of S24-7, Lactobacillus and Clostridiales in all experimental groups significantly decreased.
The sub-chronic toxicity of Nano-cerium dioxide to rats can affect the structure and abundance of intestinal microflora, long-term exposure to high doses (>100 mg/kg) causes enteritis, but there was no significant difference in the diversity of gut microbiota. Therefore, we infer that the enteritis in rats may be associated with the relative ratios of the pathogenic bacteria and intestinal probiotics, and increased of the intestinal pathogenic bacteria can disrupted intestinal homeostasis.
研究纳米二氧化铈经口亚慢性染毒对大鼠肠道毒性及对肠道菌群的影响。
将 40 只健康雄性 SD 大鼠随机分为 4 组，即对照组（去离子水）和 3 个纳米氧化铈染毒组（20、100、500mg/kg），每组 10 只。采用灌胃染毒方式，隔天染毒 1 次，共染毒 90 天。末次染毒 24 小时后，通过按压腹部收集新鲜粪便，处死大鼠，取空肠、回肠和盲肠组织进行苏木精-伊红（Hematoxylin-eosin，HE）染色病理分析。采用 Illumina NovaSeq 测序平台对大鼠粪便样本进行测序，利用 QIIME2 软件对测序结果进行分析。
组织病理学结果显示，与对照组相比，中、高剂量组大鼠的上皮组织脱落，固有层腺体结构受损或消失，黏膜中分布大量炎细胞；肠道菌群结果显示，各纳米氧化铈染毒组与对照组相比，α-多样性和β-多样性均无显著差异（P＞0.05）。与对照组相比，纳米氧化铈染毒后大鼠肠道致病菌 Mucispirillum 和 Streptococcus 显著增加，而 Weissella 减少；所有纳米氧化铈染毒组的 Akkermansia 丰度均高于对照组，但随剂量增加而降低。MetagenomesSeq 分析显示，与对照组相比，各实验组的 S24-7、Lactobacillus 和 Clostridiales 的丰度均显著降低。
纳米氧化铈亚慢性染毒对大鼠具有一定的肠道毒性，可影响肠道菌群的结构和丰度，长期暴露于高剂量（＞100mg/kg）可导致大鼠出现肠炎，但肠道菌群多样性无显著差异。因此，我们推断大鼠肠炎可能与肠道致病菌和益生菌的相对比例有关，肠道致病菌的增加破坏了肠道内的微生态平衡。
