Influence Of Molybdenum Disulfide Nanomaterials Exposure On The Intestinal Microbiomes And Metabolomes In C57 Mice

In recent years,nanomaterials and nanotechnology have been developed rapidly,of which molybdenum disulfide(MoS2)nanomaterials with a graphene-like structure have shown great application prospects due to their excellent properties,thus arousing widespread concern.At present,preliminary studies have been carried out on biological effects of MoS2 nanomaterials,but there is still a lack of systematic and thorough research on the accumulation,biodistribution and toxicity of MoS2 nanomaterials in different organs of organisms.In this study,C57 mice were used as model organisms,and mice were exposed to MoS2 for 90 days with different particle sizes(nano-sized or micron-sized)and different concentrations(2.0 mg/kg bw/day or 20.0 mg/kg bw/day).Firstly,the biodistribution and metabolic excretion of MoS2 with different particle sizes and concentrations were detected.Then the intestinal microbiomes and metabolites were detected by 16S rRNA sequencing and 1H NMR to investigate the changes of intestinal microbiota and metabolism in mice after MoS2 exposure.The conclusions are as follows:(1)Biodistribution,metabolic excretion and toxicology in mice after MoS2 exposure.The biodistribution and excretion of MoS2 in mice have significant size-and concentration-dependent manner.Although MoS2 could be excreted through urine and feces after exposure,the concentration of Mo in serum,liver,kidney,and spleen of mice exposed to with nano-low,nano-high,and micro-high concentration exposure were significantly higher than that of the control group.Nevertheless,in micro-low groups,the concentration of Mo in the organs of the mice did not increase evidently,indicating that the nano-sized MoS2 was more likely to enter the body circulation and lead to the accumulation and biodistribution in the organs of mice.Histopathological analysis showed that mucous hemorrhage and intestinal villus injury appeared in the ileum of mice in nano-low or nano-high groups,and the intestinal wall edema appeared in the colon in nano-high group.The inflammatory factors expression level of TNF-? and MCP-1 increased in intestine in nano-low,nano-high,micro-high groups,indicating that MoS2 exposure can induce intestinal inflammation.(2)Effect of MoS2 exposure on intestinal microbiomes in mice.At the level of intestinal microbiome community,the intestinal microorganism in small intestine and large intestine changed in its composition and the changes showed obvious size-and concentration-dependent manner after MoS2 exposure,and exposure to nano-high concentration had the greatest influence on the intestinal microbiome community structure.Exposure to nano-low,nano-high and micro-high concentration induced a significant increase in the proportion of Firmicutes and decrease in Bacteroidetes,resulting in a significant increase in Firmicutes/Bacteroidetes(F/B)ratio.At the level of OTU,13 and 64 distinct OTUs were found in small and large intestine microorganism in all exposured groups,and 10 unique OTUs were screened out in the intestinal microorganism in the nano-exposure groups,such as,o_Clostridiales(denovo 16885),o_Bacteroidales(denovo 173340),f_S24-7(denovo 13568)and so on.At the level of intestinal microbiome function pathways,the functional pathways involved in the small and large intestine microorganism after exposure mainly include amino acid metabolism,carbohydrate metabolism,and lipid metabolism.(3)Effect of MoS2 exposure on intestinal metabolites in mice.At the level of intestinal metabolic profiles,the metabolic profiles of the small and large intestine were changed and the changes showed obvious size-dependent manner after MoS2 exposure,the effect of nano-sized exposure were greater.At the level of intestinal metabolic molecules and metabolic pathways,there were 32 metabolic molecules in small and large intestine contents after MoS2 exposure,respectively.The metabolic pathways involved mainly include energy metabolism,oxidative stress,and amino acid metabolism.Pearson correlation analysis showed that,MoS2 exposure not only altered the gut microbiome community at the abundance level but also substantially disturbs its metabolic profiles at the function level,and the metabolic profiles of f S24-7(Bacteroidetes)in the large intestine was significantly influenced after exposure to MoS2 nanomaterials.In summary,the biodistribution and excretion of MoS2 in mice occurred significant size-and concentration-dependent manner,and the intestinal microbiomes and intestinal metabolites also developed obvious size-and concentration-dependent manner.Compared with micron materials,it reveals that MoS2 nano-materials were different with micro-materials in their biological behaviors due to obvious small size effect.Through this study,the data of intestinal microorganism and metabolism after MoS2 nanomaterials exposure are supplemented,and the understanding of the health effects of nanoscale MoS2 exposure is deepened.