Polylactic acid micro/nanoplastic-induced hepatotoxicity: Investigating food and air sources via multi-omics

Abstract

Micro/nanoplastics (MNPs) are detected in human liver, and pose significant risks to human health. Oral exposure to MNPs derived from non-biodegradable plastics can induce toxicity in mouse liver. Similarly, nasal exposure to non-biodegradable plastics can cause airway dysbiosis in mice. However, the hepatotoxicity induced by foodborne and airborne biodegradable MNPs remains poorly understood. Here we show the hepatotoxic effects of biodegradable polylactic acid (PLA) MNPs through multi-omics analysis of various biological samples from mice, including gut, fecal, nasal, lung, liver, and blood samples. Our results show that both foodborne and airborne PLA MNPs compromise liver function, disrupt serum antioxidant activity, and cause liver pathology. Specifically, foodborne MNPs lead to gut microbial dysbiosis, metabolic alterations in the gut and serum, and liver transcriptomic changes. Airborne MNPs affect nasal and lung microbiota, alter lung and serum metabolites, and disrupt liver transcriptomics. The gut Lachnospiraceae_NK4A136_group is a potential biomarker for foodborne PLA MNP exposure, while nasal unclassified_Muribaculaceae and lung Klebsiella are potential biomarkers for airborne PLA MNP exposure. The relevant results suggest that foodborne PLA MNPs could affect the "gut microbiota-gut-liver" axis and induce hepatoxicity, while airborne PLA MNPs could disrupt the "airway microbiota-lung-liver" axis and cause hepatoxicity. These findings have implications for diagnosing PLA MNPs-induced hepatotoxicity and managing biodegradable materials in the environment. Our current study could be a starting point for biodegradable MNPs-induced hepatotoxicity. More research is needed to verify and inhibit the pathways that are crucial to MNPs-induced hepatotoxicity.

Keywords: Hepatotoxicity; Metabolic disruption; Micro/nanoplastics; Microbiota dysbiosis; Transcriptomic dysregulation.

Graphical abstract

Fig. 1

Serum biochemical parameters and histological changes in the PLA MNPs-exposed groups. a–d, Serum AST (a), ALT (b), SOD (c), and T-AOC (d) in foodborne NP (FQ), foodborne MP (FR), and foodborne control (FNC) groups. e–h, Serum AST (e), ALT (f), SOD (g), and T-AOC (h) in airborne NP (AQ), airborne MP (AR), and airborne control (ANC) groups. i, Liver histology in the FQ, FR, and FNC groups. j–k, Lung (j) and liver (k) histology in the AQ, AR, and ANC groups. Black arrows point at the histological changes in tissues.

Fig. 2

Main components and alpha diversity indices of gut microbiota in foodborne PLA MNP and control groups. a–b, Major gut bacterial phyla (a) and families (b). c–e, Gut microbial richness (c), diversity (d), and evenness (e) indices. f–g, PCoA (f) and nMDS (g) plots of gut microbiota. h, Differential gut bacteria between FQ and FNC groups. i, Differential gut bacteria between FR and FNC groups. j–k, Structural gatekeepers in the FQ (j) and FR (k) gut microbiota networks.

Fig. 3

Main components and alpha diversity indices of nasal microbiota in airborne PLA MNP and control groups. a–b, Major nasal bacterial phyla (a) and families (b). c–e, Nasal microbial richness (c), diversity (d), and evenness (e) indices. f–g, PCoA (f) and nMDS (g) plots of nasal microbiota. h, Differential nasal bacteria between AQ and ANC groups. i, Differential nasal bacteria between AR and ANC groups. j–k, Structural gatekeepers in the AQ (j) and AR (k) nasal microbiota networks.

Fig. 4

Main components and alpha diversity indices of lung microbiota in airborne PLA MNP and control groups. a–b, Major lung bacterial phyla (a) and families (b). c–e, Lung microbial richness (c), diversity (d), and evenness (e) indices. f–g, PCoA (f) and nMDS (g) plots of lung microbiota. h, Differential lung bacteria between AQ and ANC groups. i, Differential lung bacteria between AR and ANC groups. j, Differential lung microbial pathways between AQ and ANC groups. k, Differential lung microbial pathways between AR and ANC groups.

Fig. 5

Metabolic and transcriptomic alterations induced by foodborne PLA NPs and MPs. a–b, Alterations of gut metabolites in the FQ (a) and FR (b) groups. c–d, Alterations of serum metabolites in the FQ (c) and FR (d) groups. e–f, Enriched gut pathways (e) and serum pathways (f) in the FQ and FR groups. g–h, Altered liver transcripts in the FQ (g) and FR (h) groups. i–j, Enriched liver GO terms FQ (i) and FR (j) groups. k, Enriched liver pathways in the FQ and FR groups.

Fig. 6

Metabolic and transcriptomic alterations induced by airborne PLA NPs and MPs. a–b, show the altered lung metabolites in the AQ (a) and AR (b) groups. c–d, Alterations of serum metabolites in the AQ (c) and AR (d) groups. e–f, Enriched lung pathways (e) and serum pathways (f) in the AQ and AR groups. g–h, show altered liver transcripts in the AQ (g) and AR (h) groups. i–j, show enriched liver GO terms in the AQ (i) and AR (j) groups. k, Enriched liver pathways in the AQ and AR groups.

Fig. 7

Correlation networks and the correlation gatekeepers in PLA MNPs-exposed groups. a–d, Correlation networks of altered microbes, metabolites, and liver transcripts in the FQ (a), FR (b), AQ (c), and AR (d) groups. e–h, Key correlation gatekeepers (larger-sized) and the correlated alternative types of components (smaller-sized) in the FQ (e), FR (f), AQ (g), and AR (h) groups.