Orally Ingested Micro- and Nano-Plastics: A Hidden Driver of Inflammatory Bowel Disease and Colorectal Cancer

Abstract

Micro- and nano-plastics (MNPLs) can move along the food chain to higher-level organisms including humans. Three significant routes for MNPLs have been reported: ingestion, inhalation, and dermal contact. Accumulating evidence supports the intestinal toxicity of ingested MNPLs and their role as drivers for increased incidence of colorectal cancer (CRC) in high-risk populations such as inflammatory bowel disease (IBD) patients. However, the mechanisms are largely unknown. In this review, by using the leading scientific publication databases (Web of Science, Google Scholar, Scopus, PubMed, and ScienceDirect), we explored the possible effects and related mechanisms of MNPL exposure on the gut epithelium in healthy conditions and IBD patients. The summarized evidence supports the idea that oral MNPL exposure may contribute to intestinal epithelial damage, thus promoting and sustaining the chronic development of intestinal inflammation, mainly in high-risk populations such as IBD patients. Colonic mucus layer disruption may further facilitate MNPL passage into the bloodstream, thus contributing to the toxic effects of MNPLs on different organ systems and platelet activation, which may, in turn, contribute to the chronic development of inflammation and CRC development. Further exploration of this threat to human health is warranted to reduce potential adverse effects and CRC risk.

Keywords: human exposure; inflammatory bowel diseases; intestinal tumorigenesis; microplastics; nanoplastics; toxicity.

Figure 1

Different approaches and techniques employed for MNPL identification and characterization [78].

Figure 2

The literature identified three significant routes for MNPL exposure: ingestion, inhalation, and dermal contact. MNPL exposure leads to the impairment of oxidative and inflammatory intestinal balance and disruption of the gut’s epithelial permeability. Moreover, the effects of MNPL exposure include dysbiosis (changes in the gut microbiota) and immune cell toxicity. MNPLs contain additives and adsorb contaminants and may promote the growth of bacterial pathogens on their surfaces. Thus, they act as potential carriers of intestinal toxicants and pathogens, which can potentially increase their adverse effects. Despite the possible impact of MNPL exposure on intestinal health and immune response that has been evidenced in vertebrates and invertebrates, there is a scarcity of studies demonstrating that these effects are relevant to humans [165]. Created with biorender.com.

Figure 3

Graphical schematization of the intestinal microenvironment in IBD patients. The intestine of IBD patients is characterized by dysbiotic microbiota (i.e., lower bacterial diversity, increased pro-inflammatory bacteria, etc.), decreased mucus layer thickness, and increased epithelial permeability, which trigger immune response activation. In this setting, antigens from dysbiotic microbes activate pro-inflammatory macrophages and dendritic cells (DCs), which release pro-inflammatory cytokines (such as TNF-α and IL-6), thus stimulating Th1 and Th17 cells and the subsequent release of other pro-inflammatory mediators and the recruitment of additional immune cells. The generation of anti-inflammatory cytokines IL-10 and IL-4 from DCs and Treg cells is also reduced [24]. Increase/exacerbation (↑); reduction (↓). Created with biorender.com.

Figure 4

MNPLs can easily accumulate in the gastrointestinal tract. As a consequence, they can exacerbate damage to the intestinal barrier in high-risk patients (for example, with inflammatory bowel diseases), in the presence of an epithelial injury (as it occurs due to lifestyle and aging), and alter intestinal flora. These effects promote plastic particle passage through the intestinal mucus and epithelial cell layers and trigger oxidative stress, inflammatory response, impaired immune function, inhibition of cell proliferation, and tissue degeneration. Colonic mucus layer disruption may further facilitate MNPL passage in the bloodstream, thus promoting the toxic effects of MNPLs on cardiac functions, microvascular sites, and distant organs. Recently, the possible link between MNPL exposure and increased colorectal cancer (CRC) has been explored, and several potential mechanisms have been proposed. It has been suggested that platelets, beyond hemostasis and thrombosis, once activated in response to tissue damage, can mediate other processes, including immune response, inflammation, fibrosis, cancer, and metastasis formation. This is mainly due to the capacity of activated platelets to extravasate, interact, and activate other cell types such as vascular and immune cells, fibroblasts, and cancer cells through direct contact and/or the release of several soluble factors and extracellular vesicles (EVs). Created with biorender.com.