Microplastic Toxicity and Intestinal Homeostasis: Insights from Microbiome and Gut Barrier Dysfunction

Global plastic production and inadequate waste management have led to widespread environmental contamination with microplastics (MPs), now detected in food, water, and air. Their small size, diverse polymer composition, and capacity to carry chemical additives and co-pollutants facilitate intestinal uptake and raise concerns about their potential impact on gut microbiota. This review synthesizes current evidence on how MPs influence gut microbial composition and function, gut barrier integrity, and associated inflammatory and metabolic pathways. We conducted a narrative review of in vivo animal studies, in vitro simulated gut systems, and human observational studies that assessed MP exposure, gut microbiota profiles, and downstream toxicological outcomes. MPs originate from primary and secondary sources and can act as vectors for metals and organic pollutants. Following ingestion, they may cross the intestinal barrier via endocytic and persorption routes, acquire a protein corona, and be recognized by immune cells, activating TLR/NF-κB, and MAPK pathways alongside oxidative stress. In these models, MP exposure induces dysbiosis, characterized by loss of beneficial SCFA-producing bacteria (e.g., Bifidobacterium, Lactobacillus, Bacteroides) and expansion of pathobionts (e.g., Escherichia/Shigella, Staphylococcus, Enterobacteriaceae), accompanied by altered bile acid metabolism. These microbiota and metabolic alterations are linked to increased gut permeability, intestinal inflammation, metabolic dysfunction, and, in some studies, reproductive and neurobehavioral effects. Current evidence supports MPs as emerging modulators of gut microbial and intestinal homeostasis. However, heterogeneity across experimental models, reliance on high exposure doses, and lack of standardized MP characterization limit robust risk assessment. These limitations underscore the need for harmonized methodologies, longitudinal large-scale human studies, and the development of targeted mitigation strategies.