稀土氧化物纳米颗粒的生物转化诱导肺部微生物群失衡

Abstract

Background Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g. , lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. Results This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G − ) bacteria, but negligible effects in Gram-positive (G + ) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G − and G + strains. La 2 O 3 as a representative REOs was demonstrated to transform into LaPO 4 on G − cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G − /G + reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La 2 O 3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G − /G + ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. Conclusions This study deciphered the distinct toxic mechanisms of La 2 O 3 as a representative REO in G − and G + bacteria and disclosed that La 2 O 3 -induced membrane damages of G − cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.