Gut Check: Microbiota and Obesity in Mice Exposed to Polystyrene Microspheres

Short abstract

Gut microbes appeared to play a role in the obesity outcomes observed in mice fed manufactured polystyrene microspheres.

Intestinal microbes are known to regulate certain aspects of metabolism in mice^1,2 and humans.³ Microplastics are one environmental exposure that can disrupt the balance of gut microbiota in mouse models.^4,5 Generally defined as plastic particles measuring $1\mathrm{\mu }\mathrm{m}$ to $5\text{mm}$ in diameter,⁶ microplastics have been documented in various human body tissues and excreta,⁷ leading to a growing interest in how exposures may affect human health outcomes.⁸

In a study recently published in Environmental Health Perspectives (EHP),⁹ scientists examined how consuming both a high-fat diet and polystyrene microspheres via drinking water might influence obesity in mice. Specifically, the study tested how the combined exposures affected multiple aspects of metabolism. The research team used a microsphere concentration that corresponded to the low end of estimated human microplastics exposure levels.¹⁰

The researchers observed, among other findings, that mice fed a high-fat diet and polystyrene microspheres had greater body weight, liver weight, adipose tissue, and serum lipid concentrations than mice on a high-fat diet only. Image: © iStock.com/Georgejason.

After 8 weeks, mice fed both a high-fat diet and microspheres had greater body weight, liver weight, and white adipose tissue mass, as well as impaired glucose and lipid metabolism, compared with mice fed only the high-fat diet. (As controls, a third group of mice was fed a normal diet; a fourth received a normal diet plus polystyrene microspheres.) The combined exposure group also showed higher levels of inflammatory cytokines and lipopolysaccharides and lower expression of mucin (Muc2) genes. Mucin is a major component of the protective intestinal mucous layer.¹¹ Further analyses indicated that gut microbiota of polystyrene-exposed mice tended to be those associated with at least one obesity parameter, such as body weight gain or accumulation of gut adipose tissue.

The team also conducted experiments in which mice were given a combination of broad-spectrum antibiotics to wipe out their gut microbes. This was followed by fecal transplant (from mice in either the high-fat diet or combined exposure group). Disrupting the microbiome eliminated obesity outcomes (e.g., weight gain, liver fat content, adipose tissue) in mice—both normal and high-fat diet groups—previously exposed to polystyrene microspheres.

Eight weeks after fecal transplant, mice consuming the high-fat diet combined with polystyrene microspheres had increases that were statistically significant in body weight, liver weight, adipose tissue, and serum lipid concentrations compared with mice consuming only the high-fat diet. The combined exposure group also showed lower expression of genes associated with intestinal integrity, including Muc2 and tight junction protein-1, or Tjp1, when compared with the control mice. These findings suggest a role for microbiota in the observed obesity outcomes.

“Intestinal dysbiosis [imbalance of gut bacteria] may undermine the integrity of the intestinal barrier, facilitating the direct translocation of lipopolysaccharides into the circulatory system,” says senior author Zhenlong Wu, a professor of animal nutrition at China Agricultural University in Beijing. Antibiotic treatment lessened the effects on gut bacteria, he explains, and thus the movement of lipopolysaccharides into the bloodstream. This explains why the groups of treated mice showed no significant differences in inflammatory cytokine levels, Wu suggests. In other words, inflammation may have resulted from dysbiosis, rather than directly from exposure to polystyrene.

“The study demonstrates that most of the diet-induced obesity and metabolic syndrome outcomes exacerbated by polystyrene microspheres [in mice] are likely mediated by changes in the composition of the gut microbiota,” says Jesus Araujo, a professor of medicine and of environmental health sciences at the University of California, Los Angeles. Araujo, who was not involved in the research, suggests that other compounds—such as probiotics, prebiotics, or compounds that could revert changes in microbial composition—could potentially inhibit or counteract the obesogenic effects of microplastics.

He notes that the authors did not actually study whether inflammation could have been caused directly by the polystyrene exposures, without involvement of inflammatory processes. In fact, there is evidence that an environmental exposure itself can lead to changes in the gut microbiome of mice, says Araujo, pointing to a mouse study of his involving ultrafine particulate matter.¹² “If the same [microbial alteration, without inflammation] occurs with polystyrene administered orally, this would support the authors’ claim,” he says.

Xiaozhong (John) Yu, a professor of environmental health at the University of New Mexico College of Nursing, underscores the importance of the findings. “This well-designed animal study applied a comprehensive experimental design, including dietary interventions, microbiota manipulation, molecular analyses, and histological assessments,” says Yu, who was not involved in the research. He emphasizes the need to understand the broader implications of microplastic pollution, “including cascading effects on human health.” However, “caution is needed when extrapolating findings to human health impacts,” he says, “due to limitations of mouse models in mirroring human responses, especially considering differences in diet, metabolism, and microbiota composition.”

Mouse-to-human extrapolation is not the only concern with interpreting this research for understanding human health of microplastics. “The use of polystyrene microspheres solves study design challenges such as reproducibility, but we are exposed to small particles with various sizes, compositions, and contaminants,” cautions EHP Editor-in-Chief Joel Kaufman, a professor in the University of Washington Departments of Environmental and Occupational Health Sciences, Medicine, and Epidemiology. “Although these early studies on microplastics that use commercial microsphere exposures are interesting, we must keep in mind that it's unclear to what degree they represent the exposures people face in their daily lives. We hope to have more realistic microplastic exposure experiments¹³ in the future.”

Biography

Wendee Nicole is an award-winning science writer based in San Diego. She is a regular contributor to Environmental Health Perspectives.