Nanoplastics Chronic Toxicity in Mice: Disturbing the Homeostasis of Tryptophan Metabolism in Gut‐Lung‐Microbiota Axis

Abstract Long‐term exposure to nanoplastics causes chronic toxicity in mammals, particularly in the gut and lung tissues. The gut‐lung‐microbiota axis plays a pivotal role in organisms through the management of gut bacteria amino acid metabolic homeostasis. However, chronic toxicity of nanoplastics from gut to lungs have yet to be fully elucidated. In this study, nanoplastics exposure not only causes colon inflammation but also results in lung fibrosis. The abundance of Akkermansia muciniphila (AKK) is decreased after nanoplastics exposure. Interestingly, a positive correlation is observed between AKK and indole‐3‐lactic (ILA). Supplementation with AKK or ILA ameliorated nanoplastics‐induced gut‐derived lung injury by restoring the balance of tryptophan metabolism. Furthermore, knocking down indoleamine 2,3‐dioxygenase 1 (ido1) upregulated ILA levels, contributing to defense against damage from nanoplastics. These results suggest that regulating ido1 expression and AKK abundance, involved in tryptophan metabolic homeostasis (especially ILA production), maybe a strategy to reduce the biological toxicity induced by nanoplastics. Mogroside V, a natural product, is found to promote AKK growth and inhibit ido1, thereby ameliorating chronic toxicity induced by nanoplastics. The study offers a new understanding of how nanoplastics cause chronic toxicity by dysregulating gut‐lung‐microbiota axis, as well as strategies for preventing and treating nanoplastics.