Gut dysbiosis exacerbates inflammatory liver injury induced by environmentally relevant concentrations of nanoplastics via the gut-liver axis

Abstract

As an emerging and potentially threatening pollutant, nanoplastics (NPs) have received considerable global attention. Due to their physical properties and diminutive size, NPs ingestion can more easily cross biological barriers and enter the human and animal body. Despite reports of hepatotoxicity associated with NPs, their impact and potential underlying mechanisms remain elusive. In this study, we investigated the impact of NPs at concentrations found in the environment on the gut flora, intestinal barrier function, liver pyroptosis, and inflammation in mice following 12 weeks of exposure. To further validate the involvement of gut flora in inflammatory liver damage caused by NPs, we utilized antibiotics to remove the intestinal flora and performed fecal microbiota transplantation. We confirmed that NPs exposure altered the gut microbiota composition, with a notable rise in the proportions of Alloprevotella and Ileibacterium while causing a decrease in the relative proportions of Dubosiella. This disruption also affected the gut barrier, increasing lipopolysaccharides in circulation and promoting liver pyroptosis. Importantly, mice receiving fecal transplants from NPs-treated mice showed intestinal barrier damage, liver pyroptosis, and inflammation. However, NPs effects on the intestinal barrier and liver pyroptosis were attenuated by antibiotics depletion of the commensal microbiota. In summary, our current research revealed that extended exposure to environmentally relevant concentrations of NPs resulted in inflammatory damage to the liver. Additionally, we have identified for the first time that imbalances in intestinal flora are crucial in liver pyroptosis induced by NPs.