Nanoplastics can disrupt gut microbes in mice by interfering with extracellular vesicle-delivered microRNA

Nanoplastics can compromise intestinal integrity in mice by altering the interactions between the gut microbiome and the host, according to a paper in Nature Communications. The study explores the complex interactions of nanoplastics with the gut microenvironment in mice.

Nanoplastics are pieces of plastic less than 1,000 nanometers in diameter, which are created as plastics degrade. Previous research has suggested that nanoplastic uptake can disrupt the gut microbiota; however, the underlying mechanism behind this effect is poorly understood.

Researcher Wei-Hsuan Hsu and colleagues used RNA sequencing, transcriptomic analysis and microbial profiling to analyze the effects of polystyrene nanoplastics on the intestinal microenvironment when ingested in mice. They found that nanoplastic accumulation in the mouse intestine was linked to altered expression of two proteins involved in intestinal barrier integrity (ZO-1 and MUC-13), which could disrupt intestinal permeability.

The nanoplastics were also shown to induce an intestinal microbiota imbalance, specifically an increased abundance of Ruminococcaceae, which has been implicated in gastrointestinal dysfunction in previous research.

These findings suggest a mechanism by which nanoplastics may affect the microbiota and the intestinal environment in mice. However, research would be needed to explore the ways in which nanoplastic accumulation could affect humans.

Wei-Hsuan Hsu, the first author of this study, is an Associate Professor from the Department of Food Safety/Hygiene and Risk Management, College of Medicine at National Cheng Kung University, Tainan, Taiwan.

“This study is the first to show that plastic particles can interfere with the microRNA carried by extracellular vesicles between mouse intestinal cells and specific gut microbes, disrupting host–microbe communication and altering microbial composition in ways that may harm the gut health of mice. The research identifies a molecular mechanism by which plastic particles disturb gut microbiota,” says Hsu.

“Since mice and humans differ in their gut microbial profiles, direct inference to human health risks is not yet possible. Long-term exposure and dose–response studies are still needed. The team has also developed a simulator of the human intestinal microbiota ecosystem to evaluate the effects of nanoplastics and other substances on human gut microbiota.”

Below, Yueh-Hsia Luo, an Associate Professor from the Department of Life Sciences at National Central University, Environmental Biomedicine Technology Center (EBMTC), College of Health Sciences & Technology, National Central University, Taiwan, discusses the study and its implications.

Why is this study important? How can it support future research on the health effects of nanoplastics in humans?

This study is the first to demonstrate that polyethylene (PE) nanoplastics can alter exosome secretion by intestinal goblet cells, thereby promoting the growth of Ruminococcaceae and contributing to gut microbiota dysbiosis. Furthermore, PE nanoplastics can be internalized by Lachnospiraceae, which subsequently secrete extracellular vesicles that inhibit intestinal mucus secretion.

These changes collectively lead to a reduction in tight junction protein expression in epithelial cells, compromising the intestinal barrier function. The mechanisms revealed in this study provide critical insights into how nanoplastics disrupt gut health and identify potential biomarkers that could serve as indicators of intestinal exposure to nanoplastics in future human health assessments.

How should the general public interpret the results of this study? Should we be concerned that nanoplastics could harm intestinal function? Do we need to change our diets?

Currently, there is insufficient evidence to suggest that typical daily exposure to nanoplastics poses a significant risk to intestinal health. The exposure levels used in this study were much higher than those humans normally encounter. Therefore, the public does not need to be overly concerned or make immediate changes to their diet based on these findings.

What are the inferential limitations of this study? Are there aspects we should interpret with caution?

While this study offers valuable insights into the biological mechanisms by which nanoplastics may affect gut health, it should not be interpreted as evidence of an immediate health threat to humans. Several important limitations should be considered when interpreting the findings:

1. High exposure dosage: In vitro effects were only observed at concentrations of 100,000 particles per mL, and the 12-week in vivo experiment involved a total exposure of approximately 10¹² particles—substantially higher than typical human exposure levels. Therefore, the findings cannot be directly extrapolated to real-world human exposure scenarios.
2. Species differences: Mouse models do not fully replicate human intestinal physiology. Differences in species-specific sensitivity and nanoplastic metabolism may limit the direct applicability of these results to humans.
3. Limited human exposure assessment: Current estimates suggest humans may ingest several hundred nanoplastic particles daily, but the proportion that falls within the nanoscale is unknown. Due to limited experimental data and the absence of established biodistribution models, it remains difficult to accurately assess nanoplastic accumulation and distribution in the human body.
4. Single material type: This study examined only one type of nanoplastic—100 nm polyethylene (PE). Since nanoplastics can vary widely in size, shape, and chemical composition, it is unclear whether the same biological effects would occur with other types of nanoplastics.

What are the most urgent research directions to confirm the potential health risks of nanoplastics to the human gut and microbiota?

Future research should prioritize the following areas:

1. Development of high-sensitivity detection methods: Establishing analytical techniques capable of accurately identifying and quantifying nanoplastics in human biological samples is essential for assessing exposure levels and potential health risks.
2. Epidemiological studies: Investigating how different populations respond to nanoplastic exposure and analyzing correlations with gut microbiota composition, immune responses, and intestinal dysfunction.
3. Realistic exposure modeling: Using animal models or human intestinal organoids to simulate chronic, low-dose exposure scenarios and track the biodistribution and metabolic pathways of nanoplastics under conditions that reflect daily human exposure.
4. Comparative studies of plastic materials: Evaluating the effects of different types of plastics on the gut to provide a more comprehensive assessment of the health risks associated with various nanoplastics.

Given the current limitations in nanoplastic detection technologies and the uncertainties associated with extrapolating animal model results to humans, continued research is critical to accurately evaluate the potential long-term health effects of nanoplastics in humans.