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Gut microbiota at the crossroads of food additives, pollutants, and chronic disease risk
Summary
This review synthesized evidence showing that microplastics, PFAS, pesticides, and food additives converge on the gut microbiota to disrupt microbial ecology, barrier integrity, and immune signaling, thereby mediating chronic disease risk. The gut microbiome framing is particularly relevant because it positions microplastic ingestion not just as a physical contaminant issue but as a driver of systemic inflammation and metabolic dysfunction through microbial disruption.
Over the past half-century, profound changes in dietary practices and environmental exposures have reshaped the human exposome, creating new challenges for public health. Rising consumption of ultra-processed foods has paralleled widespread use of artificial sweeteners, emulsifiers, preservatives, and colorants, while exposures to microplastics, per- and polyfluoroalkyl substances (PFAS), pesticides, and heavy metals have become virtually unavoidable. Mounting evidence suggests that these compounds interact intimately with the gut microbiota, perturbing microbial ecology and altering host metabolic and immune functions. Importantly, many of their biological effects are not direct but microbiota-mediated, reframing the gut as a central conduit of chemical exposure and disease risk. This review offers a novel synthesis of food additives and environmental pollutants under a unified microbiome framework, emphasizing their convergent capacity to disrupt microbial functions and propagate systemic disease risk. We examine major additive and pollutant classes, integrate mechanistic insights across barrier integrity, metabolite modulation, immune signaling, and organ crosstalk while critically appraising evidence from epidemiological and clinical studies. Microbial alterations emerge as both biomarkers and mediators of exposure effects, reframing the gut microbiota as a sensitive interface between modern lifestyles and chronic disease, underscoring the need for microbiome-inclusive risk assessment. Looking forward, the review emphasizes the urgent need for multi-omics, longitudinal, and exposome-scale studies to capture complex real-world exposures. Regulatory frameworks must evolve to incorporate microbiota endpoints, as current safety thresholds may underestimate chronic disease risks. Clinically, we propose that microbiome profiling could guide personalized nutrition and therapeutic interventions, while at the public health level, microbiota-informed policies may better protect vulnerable populations. By positioning the gut microbiota at the crossroads of diet, pollutants, and disease, this review aims to highlight both scientific opportunities and translational strategies for mitigating the hidden microbiome-related risks of modern lifestyles.