In vivo exposure of mixed microplastic particles in mice and its impacts on the murine gut microbiome and metabolome

Microplastics (MPs) are emerging environmental contaminants due to
increasing global plastic production and waste. Microplastics, defined as
plastic particles less than 5 mm in diameter, are formed through
degradation of larger plastics via sunlight, weathering, and microbes.
These plastic compounds are widely detected in water, soil, food, as well
as human stool and blood. The gut microbiome, often referred to as our
second genome, is important in human health and is the primary point of
contact for orally ingested microplastics. To investigate the impact of
ingested MPs on the gut microbiome and the metabolome, 8 weeks-old male
and female C57/BL6 mice were orally gavaged mixed plastic (5 um) exposure
consisting of polystyrene, polyethylene, and the
biodegradable/biocompatible plastic, poly- (lactic-co-glycolic acid) twice
a week for 4 weeks at 0, 2, or 4 mg/week (n = 8/group). Fecal pellets were
collected for bacterial DNA extraction and metagenomic shotgun sequencing,
and serum was subjected to targeted and untargeted metabolomics. MPs
exposure resulted in significant sex-specific and dose-dependent changes
to the gut microbiome composition along with substantial regulation of the
predicted metabolic pathways. Untargeted metabolomics in serum showed that
a low MPs dose displayed a more prominent effect on key metabolic pathways
such as amino acid metabolism, mitochondrial function, and inflammation.
Additionally, SCFA-targeted metabolomics showed significant changes in
neuroprotective SCFAs levels in both sexes by MPs exposure. In conclusion,
our study has demonstrated that microplastics dysregulate the gut
microbiome and serum metabolome, providing critical insights into
potential human disease risks associated with microplastic contamination.