Microplastics and Nanoplastics and the Digestive System

Introduction

Microplastics and nanoplastics (MNPs) arise from diverse sources and are pervasive in the environment.¹ Humans are exposed to MNPs through ingestion, inhalation, or direct skin contact. Recently, a prospective study reported an association of MNPs with cardiovascular outcomes.² Among 312 patients who underwent carotid endarterectomy, MNPs were detectable in the excised plaque of 58% of participants. Importantly, the presence of MNPs in the carotid plaque was associated with a subsequent risk of nonfatal myocardial infarction, nonfatal stroke, or death from any cause about 2 times higher compared to patients whose plaques did lack such particles.² Also, microplastics can induce insulin resistance, fatty liver, and liver fibrosis in animal models.³

To date, there is a significant gap of knowledge about the contribution of MNPs to human disease. Indeed, studying MNPs in humans is challenging for several reasons: (i) MNPs are difficult to detect and distinguish from other particles; (ii) laboratory contamination with MNPs cannot be easily contained; and (iii) standardized, affordable, and scalable methods for measuring MNPs are currently lacking.

This commentary aims to raise awareness about our exposure to MNPs and emphasizes the pressing need of human studies for better understanding the contribution of such particles to gastrointestinal and liver diseases. Indeed, the majority, if not all, mechanistic data on MNPs carried out to date and quoted in this article had emanated from in vitro or animal studies. This commentary does not discuss occupational exposures to MNPs.

Definition and Origin of Microplastics and Nanoplastics

Microplastics are defined as plastic particles smaller than 5 mm. Nanoplastics are even smaller, measuring less than 1 mm in size.¹ MNPs are widespread in the environment, particularly in bodies of water (ie, oceans, lakes, and rivers) as well as in the food chain and air.¹ MNPs originate from the breakdown of larger plastic items, such as bottles and containers, in the presence of environmental factors (ie, high temperature, UV radiation) or due to the direct release of small plastic particles from household products, personal care products, or polymeric raw materials. Microplastics can be characterized based on shape, colors, and type of polymer they are made of.⁴ Since the 1950s, more than 9000 million tons of plastics have been produced and accumulated in our environment.⁵ Current estimates indicate that almost 400 million tons of plastics are produced yearly, and this number is projected to triple by 2060.⁵ Presently, about 40% of plastic production is made for single-use plastic (ie, syringes, gloves, supermarket plastic bags), and only 10% of produced plastics are recycled. Plastics contain more than 16,000 chemicals and nearly 80% of those have never been tested for safety and toxicity.⁵

Cellular Uptake and Effects of Microplastics and Nanoplastics on the Intestine and Liver

The intestine is one of the main portals of entry for MNPs in the human body. It is estimated that the average person ingests 39,000–52,000 microplastics alone annually or, in weight, the equivalent of a credit card.⁶ A major site of entry upon ingestion of MNPs is the Peyer’s patches of the intestine.¹ However, microplastics have been found in every organ and tissue (Figure). MNPs often enter cells through passive penetration or endocytosis.⁷ Once internalized, these particles can remain within the cytoplasm or be sequestered in endosomal compartments. Once in the cytoplasm, MNPs can translocate to various organelles and may even be transported along cytoskeletal structures (eg, microtubules) to travel throughout the cell.⁸ This cytosolic mobility further aids their distribution across different cellular compartments bypassing exocytosis. Also, nanoplastics may evade phagocytosis by macrophages due to their size and surface properties that do not trigger such elimination processes.⁷ The uptake of MNPs by dendritic cells can drive the presentation of antigens, activating T-cells and possibly resulting in altered immune homeostasis. This perturbation may contribute to gastrointestinal disorders and systemic inflammation, suggesting a complex interplay between MNPs and the immune system.

Figure.

Sources and presence of microplastics. Microplastics exist in nearly all tissues although at different concentrations. MP, microplastics.

MNPs naturally acquire coatings (eg, proteins, lipids) that mask their presence from the immune system, reducing the likelihood of detection, and subsequent immune responses for their elimination. Exposure to nanoplastics may modulate inflammatory pathways, resulting in an immunosuppressive environment. Exposure to MNPs can lead to oxidative stress through the generation of reactive oxygen species (see below). The oxidative stress may be overwhelmed, leading to cell damage and inflammation.

Damage and Crossing of the Gastrointestinal Tract and Alteration of Gut Microbiome

Fourier transform infrared spectroscopy analyses of human feces showed evidence of microplastics excretion via the gastrointestinal tract.⁹ Based on data from mammalian and aquatic models, ingested microplastics, owing to their size, largely remain in the intestinal tract and excreted through feces. However, smaller microplastics (<20 μm) and sub-microsized plastic particles can be absorbed by the gut and retained in circularly fluids. The very small particles (eg, <100 nm) and nanoplastics are readily absorbed by the gut and capable of penetrating cells.¹ Microplastics were ubiquitously present in the human colon, as shown in a study of sequential colectomies.¹⁰ Indeed, polyethylene microplastics reported to trigger inflammation in the intestine of mice.¹¹ Mucosal colon tissue of inflammatory bowel disease patients showed greater than 2-fold increased transport of microplastics found on human colectomy specimens. Upon crossing the intestinal lumen, microplastics could be engulfed by dendritic cells and transported through lymphatics in the systemic circulation.

The widespread distribution of MNPs in ecosystems can also impact human health through effects on gastrointestinal microbiota. However, the mechanisms through which microbiome alteration occurs remain poorly understood. Studies showed that microplastics modulate the composition and diversity of human microbiota in a manner that may promote inflammation and immune dysfunction of the gut. Specifically, exposure of the human digestive tract to microplastics resulted in a reduction of Bacteroides and Parabacteroides colonic communities. These are beneficial species of human microbiota with anti-inflammatory and epithelium-reinforcing properties.¹² In addition, microplastics resulted in increased proportions of Escherichia/Shigella bacterial groups whose enrichment in gut microbiome has been associated with inflammatory bowel disease.¹³ Collectively, microplastics-induced changes in colonic microbial communities may impair the gut microbiome homeostasis in a manner that compromises epithelial integrity and promotes inflammation. Further research is needed to better elucidate the fate of microplastics in the intestinal tract and their relationship with intestinal dysbiosis, immunological dysfunction, and risk of disease.

Oxidative Stress, Metabolic Dysfunction, and Immune Responses of the Liver

In zebrafish, microplastics exposure and accumulation increased activity of antioxidant enzymes, inflammation, and lipid accumulation, as well as altered metabolic profile in the liver. Some marine species have been utilized to examine toxicological responses to nanoplastics exposure, which led to liver lipid metabolism disorders that consequently decreased growth and survival rate.¹⁴ In mice, microplastics caused a significant decrease in ATP production in the liver, resulting in reduced lipid metabolism.¹⁴ Thus, microplastics might increase food intake in rodents as a response to higher energy demands or lower absorption efficiency. It is therefore possible that in humans, microplastics may cause similar metabolic disruptions by modulating energy expenditure, decreasing nutrient intake, and/or altering synthesis and activity of metabolic enzymes. Hepatocytes can internalize MNPs through several mechanisms, including receptor-mediated endocytosis. Also, MNPs may disrupt mitochondrial function within hepatocytes, leading to reduced ATP production—a critical energy source for cellular processes.¹⁵ Mitochondrial impairment caused by MNPs can significantly affect ATP synthesis. A decrease in ATP reduces the ability of hepatocytes to perform essential metabolic tasks, which can lead to dysregulation of lipid metabolism. For example, ATP is necessary for processes like fatty acid oxidation and lipogenesis; thus, reduced ATP levels can lead to an increase in hepatic fat accumulation, contributing to conditions like metabolic dysfunction-associated steatotic liver disease.

Microplastics can induce systemic and/or local immune responses depending on their tissue distribution including the liver. Chronic liver disease could be a central driver in microplastics accumulation within hepatocytes and it remains yet unknown whether their accumulation is a contributor of liver fibrosis or cirrhosis. This may be caused by oxidative stress of cells, the release of immune modulators, or the inappropriate activation of immune cells, with implications to induce autoimmune disorders. For instance, microplastics can be internalized by macrophages, which play a major role in mediating acute immune responses.¹⁶

Carriers for Toxic Substances, Microbes, Antibiotics, Effects on the Digestive System and Risk for Antimicrobial Resistance

MNPs have been reported to function as carriers of persistent organic pollutants, heavy metals, microbes, and antibiotics through surface adsorption as well as adhesion. Organic pollutants such as aromatic hydrocarbons, chlorohexanes, benzenes, perfluoroalkyl, and pesticides substances are present in MNPs. Heavy metals, such as cobalt, cadmium, lead, nickel, and copper, are the most common contaminants transported by MNPs. Microplastics can also impact human health through the risk of antimicrobial resistance (AMR) because they provide a favorable surface for the attachment of microbes. Indeed, a large number of multiantibiotic-resistant bacteria were discovered in microplastics samples with concentrations 100–5000 times higher compared with water samples.¹⁷ A study in Nine Rivers, IL, reported a higher presence of Pseudomonas spp. on microplastics than on other organic material or in water.¹⁸ Microbiota associated with microplastics, the plastisphere, constitutes an ideal niche for formation of biofilms with highly concentrated bacteria. Dense bacterial communities on microplastics facilitate cell-to-cell communication and horizontal transfer of AMR genes¹⁷ influencing the resistome and potentially enhancing the spread of AMR. Although drinking water treatment can effectively remove most of microplastic particles, the cumulative impact of microplastics on the transfer and evolution of AMR remains unclear. AMR renders antimicrobials ineffective and is a major threat to modern medicine, with a projected burden of 10 million annual deaths globally by 2050.¹⁹ Ineffective antimicrobials will impair our ability for appropriate surgical antibiotic prophylaxis or treatment of patients vulnerable to infections (eg, organ transplant, cirrhosis, malignancy, pregnancy). The intersection of microplastics and AMR underscores the importance of One Health, a multidisciplinary approach that addresses environmental and health challenges integrating research, policy, and public awareness initiatives.²⁰

Gaps of Knowledge, Future Research, and Advocacy

The increasing production, use, and pollution caused by MNPs, and their potential contribution to human disease, demand our awareness and attention. However, there are not enough data regarding their potential health effects. A systematic epidemiological evaluation of the biological impact of MNPs on humans (ie, immune responses, inflammation, oxidative stress) over time is urgently needed. The US Agency for Toxic Substances and Disease Registry formed an MNP work group in partnership with the Centers for Disease Control and Prevention’s National Center for Environmental Health to assess human health risks from MNPs.²¹ Thus far, the overall scientific evidence does not support that the present levels of MNPs found in food pose a risk to human health for the Food and Drug Administration to take regulatory action.

Nevertheless, the Centers for Disease Control and Prevention and Food and Drug Administration continue to monitor the ongoing research studies on MNPs recognizing the current significant gaps of knowledge. Lack of standardized definitions as well as sample collection and preparation, sparse reference materials, variability of analytical methods, and limited appropriate quality controls are some of the reasons for our restricted knowledge at the present time. Also, the California State Water Resources Control Board has taken the first step toward quantifying the risk to people’s health by announcing standard methods for measuring microplastic concentrations in drinking water.²² Moreover, on July 19, 2024, the US government released a new strategy to tackle plastic pollution (Link). Of interest, about 25% of the waste generated daily by US hospitals is due to plastics, and the vast majority of those are not recycled.²³ Of note, gastroenterology-hepatology as a specialty is responsible for 13,500 tons of plastic waste in the US per year, making it the third highest generator of waste in the hospital setting.²⁴

To this end, we support the regulatory frameworks that will seriously consider banning polycarbonate and polystyrene in medical devices due to their endocrine-disrupting and neurotoxic properties, respectively. The distinct leaching behaviors of these materials underscore the urgency for policy changes that favor safer alternatives, ultimately aiming to protect public health while ensuring the efficacy of medical devices.

On the other hand, the use of polystyrene-based laboratory consumables and cell culture ware in in vitro studies presents certain limitations, especially concerning the study of MNPs. Using glass-made laboratory consumables instead of plastic offers several advantages, including reduced background interference from leachates and greater compatibility with a range of solvents and chemicals. Glass surfaces may also provide more physiologically relevant environment for studying cell biology.

Healthcare professionals need to be aware of the potential dangers of MNPs and educate patients about reducing the use of plastics. Practical measures to reduce plastic production and exposure for individuals include (1) using of reusable bags, bottles, and containers that are made of nonplastic material (ie, cloth, paper, glass, metal); (2) reading labels and minimize or avoiding products containing MNPs; (3) planning meals to reduce the use of plastic wraps and containers for food storage; and (4) staying informed about plastic pollution and advocating for local policies that promote sustainable practices. Actions for industries to reduce plastic use and pollution include (1) transitioning to biodegradable, compostable, or recyclable materials; (2) innovating products to be more durable, reusable, and repairable; (3) reducing dependence on single-use plastics; and (4) raising awareness about the environmental impact of plastics and promoting responsible consumption behaviors.²⁵ Without doubt, there is an urgent and important need to better understand whether and how MNPs impact the digestive system and diseases.

Conclusion

The digestive system is one of the most exposed to MNPs daily. As healthcare professionals and scientists specializing in the digestive diseases and studying the digestive system we are obligated to further investigate the role and effects of MNPs on the illnesses we are concerned with for the benefit of the public and our patients.