The Plasticene Paradigm: Microplastics, Gut Dysbiosis, and Food Allergy — A Critical Commentary

Abstract

Background The increasing prevalence of food allergy (FA) in industrialized regions cannot be fully explained by traditional hygiene and biodiversity frameworks, suggesting the involvement of new environmental triggers. Microplastics (MPs), which are dietary contaminants now consistently found in human biological samples, have been proposed as a potential threat to gut-immune balance. However, direct evidence for this link in humans is still lacking. Main Body This commentary critically examines and advances the “Plasticene Paradigm”, which hypothesizes that dietary MP exposure disrupts the beneficial relationship between the host and its microbiota, thereby promoting the development of FA through microbiota-dependent mechanisms. The central mechanism proposed involves MP-induced dysbiosis, characterized by a reduction in short-chain fatty acid (SCFA) -producing bacteria. This reduction subsequently impairs the differentiation of regulatory T cells (Tregs), disrupts the balance between Th2 and Treg cells, and compromises the integrity of the intestinal barrier. While studies involving fecal microbiota transplantation in animal models offer causal evidence under experimental conditions, this evidence primarily comes from studies using supraphysiological doses of pristine polymers (mg/kg/day range). These doses exceed mass-based estimates of human daily intake (μg/kg/day range) by several orders of magnitude, although direct quantitative comparison is complicated by the use of heterogeneous exposure metrics (mass-based vs particle-count-based) across different estimation approaches. This significant difference in dosage fundamentally limits the applicability of these findings to human exposure levels found in the environment. We identify four obstacles to translating these findings: dose relevance, exposure complexity, challenges in model extrapolation, and analytical constraints. These barriers currently prevent drawing definitive conclusions about human risk. Conclusion The current evidence, which is predominantly preclinical, is constrained by issues of dose relevance, exposure complexity, and gaps in model extrapolation, with human data largely showing only associations. We propose a three-pronged research agenda: (I) establishing prospective birth cohorts with specific biomonitoring for polymers; (II) conducting mechanistic studies using environmentally relevant MP mixtures in FA models; and (III) developing microbiome-targeted interventions as needed. This framework aims to transform the Plasticene Paradigm from a hypothesis-driven mechanistic narrative into one supported by a stronger evidence base. This evidence may ultimately inform public health policy, food safety regulations, and precise prevention strategies for FA in an era of widespread plastic contamination.