Plastics are widely used in modern society; every year ~320 tons of plastics are manufactured globally (1). Plastics are used in a wide range of applications, including packaging materials, construction, automotive parts, electronics, medical devices, textiles and consumer goods, due to their versatility, durability and cost-effectiveness. These plastic products are usually resistant to high temperature, acid, alkali and corrosion and have the benefit of convenience due to their lightweight nature, ease of manufacturing, versatility and cost-effectiveness in various applications. However, there is no efficient and feasible method for plastic degradation, which results in notable environmental issues. The most common plastic pollutants in the environment include polyethylene, polyvinyl chloride, polypropylene, polyethylene terephthalate and polystyrene (2). In the natural environment, these plastics are rarely completely degraded by microbiological activity, radiation and mechanical stress, leading to disintegration and fragmentation of larger plastic items into smaller particles; transfer and diffusion are more likely to occur, resulting in microplastic (MP) pollution of the environment.

Plastic particles are divided into MPs with diameter <5 mm and nano-plastics (NPs) with diameter <1 µm. MPs are found in a range of environmental domains, including air, fresh water, soil and oceans (3). MPs are released in numerous ways, for example as microfibers from textiles during washing and from synthetic textiles, personal care products, synthetic rubber tire erosion and industrial production. After a series of environmental processes such as decomposition and migration, they enter animals and plants, and enter the human body via inhalation, ingestion and skin contact (4). Ingestion of MPs or plastic derivatives such as chemical additives can cause a variety of toxicological effects, including growth inhibition, metabolic disorder, inflammatory response, reproductive problems and mortality (5,6).

Studies have found MPs and NPs are present in human blood, placenta and feces (7–9). The ingestion of MPs is a prevalent route of exposure, with MPs being detected in food and beverages such as seafood, drinking water and beer (4). Exposure models in mice have shown that MPs and NPs accumulate in the stomach, intestine, liver and other organs (10,11). Due to the high corrosion resistance of MPs and NPs entering into the digestive tract, digestive fluid changes the surface roughness and particle size of MPs and NPs, making them more stable in the lining of the digestive tract and more prone to adsorption of toxic substances (12). The barriers within the tissues do not prevent invasion of MPs and NPs. After MPs and NPs enter the body, small plastic particles can cross the epithelial barrier of the digestive system (13–15) and enter the lymphatic and blood circulation. For example, NPs with a size of 0.1–10 µm cross the blood-brain barrier and the placenta (16–18). Ingested MPs and NPs with a particle size >150 µm pass through the intestinal epithelial cells with difficulty, resulting in ~90% of MPs being excreted through feces, with the rest having a localized effect outside the intestinal epithelial cell membranes. When nanosized plastic particles with diameter <150 µm come into contact with the villi of the small intestine, they pass through the small intestinal epithelial cells (19), enter the lymphatic system (20) and bloodstream (21), and reach the portal vein through the capillaries and are spread throughout the body (22–24). NPs with diameter <150 and >10 µm reach other organs and cell membranes (17), while those with a size of <5 µm are absorbed by lymphocytes (19). Smaller nanoparticles diffuse into the bloodstream via bypass of intercellular tight junctions (25). Mucus secreted by the intestinal epithelial cup cells promotes bypass diffusion of the nanoparticles (19). Larger nanoparticles (diameter, 50–200 nm) tend to cross intestinal epithelial cells by endocytosis; 40 nm diameter may be the optimal size for non-phagocytic uptake (26), while 200 nm may be the optimal size for crossing the blood-brain barrier (27). In vivo studies have found that intestinal cells internalize nanoscale particulate matter using different endocytosis mechanisms; additionally phagocytes can internalize them through phagocytosis (28), whereas non-phagocytes internalize smaller nanoparticles with the help of lattice proteins or cell-membrane-invasion-mediated endocytosis (25), in which actin serves an important role (29). In addition, energy-dependent pathways serve a key role in the mechanisms of endocytosis in intestinal epithelial cells (29). NPs smaller than 3 µm can be internalized into non-phagocytic cells via non-specific endocytosis (29), while the maximum particle size available for endocytosis increases to 5 µm (19), facilitated by the abundant M cells in the intestinal Peyer's patches (21) and aided by the intestinal mucosal membranes (30,31). The strong electrostatic interaction between positively charged particles and the plasma membrane increases surface tension, which subsequently reduces the membrane's elasticity (32), facilitating NPs internalization and their entry into the bloodstream. In addition to NPs absorbed by the digestive tract, inhaled MPs and NPs remain in the lungs or enter the circulatory system through capillaries; particles with a size of <2.5 µm enter the circulation or penetrate the alveoli (33). NPs that enter the circulation (diameter, ~100 nm) are surrounded by serum albumin (34), forming a multilayered serum albumin crown, which may help the NPs evade immune surveillance, increase their time in the circulatory system and help the particles reach secondary organs and accumulate in the liver, kidneys and intestines (34). The binding of serum albumin to NPs leads to changes in the secondary structure of the protein (35), which increases cytotoxicity of the plastic particles.

Although only a small percentage of NPs penetrate the epithelial barrier of alveolar and gastrointestinal tracts, and transfer into secondary tissues and organs (9), this low rate of internalization may have considerable consequences due to long-term exposure of humans to plastic particles and the potential of accumulation; harmful effects include oxidative stress, local inflammation, cellular apoptosis and alteration of intestinal flora (36–39). An in vivo study showed that following MP ingestion by mice, interaction between Helicobacter pylori and MPs in the stomach promoted the rapid colonization of H. pylori in the epithelial cells of the gastric mucosa (10); proliferation of this pathogenic bacterium leads to stomach inflammation in the mice. In several in vivo studies, MPs were found to cause intestinal flora disorders in mice, with an increase in number of conditionally pathogenic bacteria, accompanied by intestinal inflammation (40–42). The effects of NPs on the liver mainly include disruption of glycolipid metabolism, with an increase in glucose and diabetes mellitus in NP-exposed mice (43) and a decrease in hepatic fat, triglycerides and total cholesterol (44). An in vitro study has found that NPs enter cells and lead to injury effects (45). Co-culture of human gastric mucosal epithelial cells with NPs results in decreased proliferation and increased apoptosis (46). NPs cause oxidative stress in human intestinal cells (47).

To the best of our knowledge, there are no studies investigating whether MPs and NPs pass through the food chain to the human body; however, in vitro and ex vivo studies reveal the adverse effects of MPs and NPs in the human body (4,8,9). Investigating the mechanism of injury effects of MPs and NPs is key for understanding the impact of MPs and NPs on health, as well as for prevention and treatment of MP- and NP-induced health problems.

The present review discusses the mechanisms by which MPs and NPs damage the human gastrointestinal tract and liver and limitations of existing research and suggests future research directions to provide a scientific foundation for investigation of the effects and mechanisms of MPs and NPs on the human body.

A comprehensive online search using PubMed (https://pubmed.ncbi.nlm.nih.gov/), Embase (https://www.embase.com/), the Cochrane Library (https://www.cochranelibrary.com/) and the International Clinical Trials Registry Platform (https://clinicaltrials.gov/) was performed from their inception to January 2024 with the following MeSH and EMTREE keywords: ‘Micro-plastics’, ‘nano-plastics’, ‘gastrointestinal disease’, ‘liver/hepatic metabolism’, ‘MPs’, ‘NPs’ and ‘digestive diseases’. All published studies associated with MPs and/or NPs, gastrointestinal disease or liver metabolism were included. Studies were excluded if they did not focus on MPs and/or NPs in the context of gastrointestinal diseases or liver metabolism, or if they were not published in peer-reviewed journals. Two independent investigators conducted the literature searches and eligibility assessment, and discrepancies were resolved by consensus and consultation with a third reviewer.

MPs and NPs enter cells through endocytosis mechanisms or become adsorbed and accumulate on the surface of gastrointestinal tissue, causing oxidative stress, inflammation and apoptosis (Tables I and II). Therefore, it is important to investigate the mechanism underlying injury effects of MPs and NPs on the gastrointestinal tract to provide a scientific basis for prevention and treatment of gastrointestinal diseases caused by MPs and NPs.

The liver is a key detoxification organ in the human body. MPs and NPs accumulate on the surface of epithelial cells in the gastrointestinal tract following ingestion. NPs are absorbed by epithelial cells and they then enter the lymphatic and blood circulation, arriving at the liver through the portal vein (62). Study has also found that NPs disturb the glucose-lipid metabolism of liver tissues (63), and similar toxic effects have been detected in an in vitro study of human liver-like organs. Toxic effects of NPs were also found in in vitro human liver-like organs (6). Previous biochemical and transcriptomics studies have investigated the injury mechanism of NPs causing disruption of glycolipid metabolism in liver tissue (11,43,57) and found that NPs affect glycolipid metabolism at both biochemical and transcriptional levels. NPs cause injury due to effects on intermediate glycolipid metabolism at the biochemical level and production of key rate-limiting enzymes in glycolipid metabolism at the transcriptional level.

As MPs and NPs are widely located in the biosphere, their impact on human health is of concern. Studies have demonstrated that humans are continuously exposed to MPs and NPs by inhalation or ingestion (4–6). When MPs and NPs enter the human body, larger particles are eliminated in feces, while smaller particles are processed by gastric juices and intestinal mucus, accumulating in the gastrointestinal tract (84) where they are absorbed into the cells (16). Current research suggests that a small proportion of particles cross the lung and intestinal barriers and accumulate in tissues and organs. Particles with diameter <150 µm are able to travel from the intestinal lumen to the lymphatic and circulatory system, accumulating in tissues throughout the body, including the liver, kidney and brain, producing various toxic effects (62). MPs and NPs induce oxidative stress in cells by two methods: Direct stimulation of intracellular ROS production and inhibition of antioxidant enzymes and GSH synthesis, resulting in ROS metabolism (50). The inflammatory response in the gastrointestinal tract is primarily induced by direct stimulation of phagocytosis to secrete proinflammatory cytokines and disruption of intestinal bacterial flora, which leads to an increase in the number of conditionally pathogenic bacteria (41). Inflammation, oxidative stress and DNA damage caused by NPs entering cells activate the apoptotic signaling pathway, leading to cell death. At the biochemical level, NPs mainly affect the production and metabolism of glucose, triglycerides and fatty acids, while at the transcriptional level, NPs primarily affect production of rate-limiting enzymes of glycolipid metabolism, leading to disorders of glycolipid metabolism. The gastrointestinal toxicity effects of MPs and NPs and effects on hepatic glucose metabolism increase the risk of gastroenteritis, hyperglycemia, diabetes mellitus, hepatic hypertrophy, hyperlipidemia and lipodystrophy, posing a threat to human health (79).

Studies on toxic effects and mechanisms of MPs and NPs on the gastrointestinal tract and liver are based on human cells, rodents and aquatic species (43,59). Although the aforementioned studies have provided evidence of the possible toxic effects of MPs and NPs on the gastrointestinal tract and liver in humans, there is lack of knowledge regarding the absorption, metabolism and excretion of MPs and NPs in the human body. Additionally, the ability of MPs and NPs to cross the human tissue barrier is unclear; further studies are needed to investigate the mechanisms by which MPs and NPs cross the gastrointestinal barrier and the mechanisms underlying the toxic effects caused by MPs and NPs. Studies have found that MPs and NPs impair intestinal barrier function by decreasing intestinal mucus secretion, inhibiting synthesis of tight junction proteins, increasing intestinal permeability and causing disruption of intestinal flora (38,41,47). To the best of our knowledge, however, there is still a lack of research on the specific mechanisms by which MPs and NPs impair the gastrointestinal barrier.

In vitro studies investigating the toxic effects of MPs and NPs on the gastrointestinal tract and liver use concentrations of MPs and NPs that are higher than the actual concentrations humans are exposed to in real life (15,20,30). Therefore, there is a need to understand the toxic metabolism kinetics of MPs and NPs within the context of the actual concentrations to which humans are exposed. Furthermore, there are differences in the immunological capacity and immune status between individuals that should be considered when assessing toxicological effects in humans.

An increasing number of studies have found that MPs and NPs affect the immune system, as evidenced by the induction of intestinal flora dysbiosis by MPs and NPs, leading to immune imbalance and uptake of NPs by lymphocytes (40,57,85). However, studies of toxic effects of MPs and NPs on immune cells are limited, and there is lack of studies investigating the toxic effects of MPs and NPs on the immune system as a whole (59). The gut microbiota, which is not only an important component of immune and metabolic health but also affects the central nervous system, has been shown to communicate through several pathways of the ‘brain-gut axis,’ as identified using animal models (44,63,86). Therefore, the toxic effects and mechanisms of MPs and NPs on the brain-gut axis following gut flora disruption should be further investigated.

The gastrointestinal tract and liver are key organs for absorption, metabolism and detoxification. The harmful effects of MPs and NPs involve the intestinal-hepatic axis, causing oxidative stress, inflammation, apoptosis and disorders of hepatic glucose and lipid metabolism in the gastrointestinal tract, resulting in gastroenteritis, hyperglycemia and hyperlipidemia (43). MPs and NPs also indirectly affect the brain-gut axis through the intestinal flora. Therefore, the toxic effects of MPs and NPs on the gastrointestinal tract and liver and their mechanisms should be investigated further.