Dietary Micro- and Nanoplastics and Gastrointestinal Carcinogenesis: Mechanistic Insights, Toxicological Evidence, and Critical Knowledge Gaps

The widespread presence of micro- and nanoplastics (MNPs) in food, their increasing detection in human tissues, and growing evidence of dietary exposure have raised concerns regarding their potential impact on human health. Although the carcinogenic potential of MNPs has not yet been established in human populations, mechanistic studies have identified effects on biological pathways relevant to carcinogenesis. This review summarizes current knowledge on dietary and systemic exposure to MNPs and evaluates the strength and limitations of the evidence linking MNP exposure with gastrointestinal carcinogenesis, with particular emphasis on colorectal cancer (CRC). Recent studies have demonstrated the presence and accumulation of microplastics in human tissues, including colorectal tumor samples, indicating internal exposure but not establishing a causal relationship between MNP exposure and tumor development. Experimental studies indicate that MNPs may promote oxidative stress (OS), DNA damage, chronic inflammation, mitochondrial dysfunction, epigenetic alterations, and disruption of gut microbiota homeostasis, all of which are biological processes implicated in carcinogenesis. The biological effects of MNP appear to depend on their physicochemical characteristics, including particle size, polymer composition, surface properties, and associated chemical contaminants. The integration of exposure data with mechanistic evidence supports the biological plausibility of MNP-associated effects relevant to gastrointestinal carcinogenesis. However, much of the current evidence relies on in vitro and animal models using exposure conditions that may not fully reflect chronic, environmentally relevant human exposure. Crucially, major knowledge gaps remain, particularly regarding human epidemiological evidence, long-term exposure assessment, analytical limitations, and evidence for causality. Future research should focus on standardized analytical approaches, longitudinal studies, physiologically relevant exposure models, and an improved understanding of how specific MNP characteristics influence molecular pathways associated with carcinogenesis.