Current studies simply focus on the toxicity of nano-plastics, while the correlation between their toxicity and bio-distribution, as well as intestinal microorganisms is still blank. Therefore, we systematically evaluated the toxicity based on the accumulation characteristics of nano-plastics in C. elegans. Meanwhile, for the first time, human fecal microbiota was transplanted into the gut of C. elegans and found that nano-plastics can through the intestinal barrier to the whole body after oral intake and can't be drastically excreted until die, thus causing toxic effects; while human fecal microbiota transplantation can significantly improve the living state via activating PMK-1/SKN-1 pathway to promote the production of intracellular glutathione, and exogenous glutathione addition can also markedly protect nematodes against nano-plastics induced toxicity. Our results not only provide a fully understand between the accumulation characteristic and health risk of nano-plastics, but also take C. elegans and intestinal flora into the field of toxicity evolution of nanomaterials.