Wu Yanliang, Yao Yongrong, Shen Ye, Bai Hangjia, Zhang Louqian, Zhang Chaofeng
Sino-Jan Joint Lab of Natural Health Products Research, Department of Chinese Medicine Resources, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, 210009, China.
School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Small. 2025 Jul;21(26):e2412286. doi: 10.1002/smll.202412286. Epub 2025 May 12.
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.
长期暴露于纳米塑料会导致哺乳动物出现慢性毒性，尤其是在肠道和肺组织中。肠-肺-微生物群轴通过管理肠道细菌氨基酸代谢稳态在生物体中发挥关键作用。然而，纳米塑料从肠道到肺部的慢性毒性尚未完全阐明。在本研究中，纳米塑料暴露不仅会导致结肠炎症，还会导致肺纤维化。纳米塑料暴露后，嗜黏蛋白阿克曼氏菌（AKK）的丰度降低。有趣的是，观察到AKK与吲哚-3-乳酸（ILA）之间存在正相关。补充AKK或ILA可通过恢复色氨酸代谢平衡来改善纳米塑料诱导的肠道源性肺损伤。此外，敲低吲哚胺2,3-双加氧酶1（ido1）可上调ILA水平，有助于抵御纳米塑料造成的损伤。这些结果表明，调节参与色氨酸代谢稳态（尤其是ILA产生）的ido1表达和AKK丰度，可能是降低纳米塑料诱导的生物毒性的一种策略。罗汉果甜苷V是一种天然产物，被发现可促进AKK生长并抑制ido1，从而改善纳米塑料诱导的慢性毒性。该研究为纳米塑料如何通过失调肠-肺-微生物群轴导致慢性毒性提供了新的认识，以及预防和治疗纳米塑料的策略。
