Commentary on “Polyethylene terephthalate microplastics exposure enhances the risk of ulcerative colitis: insights from multiomics integration, machine learning, and molecular docking reveal intestinal toxicity mechanisms”

We read with great interest the article by Yang et al[1], published in the International Journal of Surgery entitled “Polyethylene terephthalate microplastics exposure enhances the risk of ulcerative colitis: insights from multiomics integration, machine learning, and molecular docking reveal intestinal toxicity mechanisms.” This study represents a valuable exploration into uncovering the association between polyethylene terephthalate microplastics (PET-MPs) and ulcerative colitis (UC), as well as their underlying molecular mechanisms. For the first time, the authors integrated interdisciplinary techniques including multiomics, machine learning, and molecular docking to identify four hub genes – CTSK, NAAA, PDE4B, and PFKFB3 – and ultimately validated the exacerbating effect of PET-MPs on intestinal inflammation through animal experiments, shedding light on the correlation between pollutants such as plastics and the pathological mechanisms of ulcerative colitis. We sincerely commend the authors for their innovative contributions in study design and technical application. Beyond their findings, we aim to put forward several supplementary considerations focusing on the completeness and rigor of the animal experimental design, with the goal of further enhancing the reliability and clinical translational value of the research conclusions. This commentary also adheres to the provisions of the 2025 TITAN Guidelines regarding the declaration and use of artificial intelligence in scientific manuscripts[2]. First, regarding the experimental grouping, it is recommended to add a standalone PET-MPs exposure group. The current study includes three groups: the control group, the DSS-treated group, and the DSS + PET-MPs co-administration group, but lacks a “PET-MPs gavage alone + normal drinking water” group. Consequently, it is challenging to clarify whether PET-MPs directly induce UC or merely exacerbate DSS-induced inflammation – specifically, the independent pathogenic role of PET-MPs in the absence of pre-existing intestinal damage remains undetermined. Adding a standalone PET-MPs exposure group would help establish a direct causal relationship between PET-MPs and UC, further validating the core conclusion that PET-MPs increase the risk of UC. Second, the current evidence base is primarily limited to observing the effects of a single PET-MP exposure dose (0.5 mg per mouse), with no systematic investigation across multiple dose gradients. This limitation may hinder the quantitative assessment of the risk of UC induced by PET-MPs. A core principle of toxicological research is to reveal the hazard threshold and intensity of pollutants through dose–response relationships[3]. Future studies are advised to incorporate comparative analyses of low, medium, and high dose groups, combined with multi-dimensional indicators such as hub gene expression levels, inflammatory factor concentrations, and pathological scores. Such an approach will facilitate the establishment of a more precise and clinically translatable quantitative understanding of PET-MP-induced UC risk, providing a scientific basis for environmental exposure risk assessment. Furthermore, as a chronic inflammatory disease in clinical practice, UC is characterized by an insidious onset and chronic progressive course[4]. Short-term exposure experiments are relatively unable to simulate the actual scenario of long-term human exposure to microplastics. In this study, the intervention period was set at 7 days, which is relatively short and not conducive to observing the effects of PET-MPs on intestinal inflammation, mucosal damage, intestinal microecology, and other aspects. Future studies should include a long-term observation phase, which will help establish a more comprehensive evidence base for the role of PET-MPs in the pathogenesis of UC. In summary, Yang and colleagues’ rigorous research provides valuable evidence for the association between PET-MP exposure and UC, as well as the underlying molecular mechanisms. However, addressing the three aforementioned limitations would enhance the scientific rigor and clinical translatability of future studies. We appreciate the authors’ significant contributions and look forward to more comprehensive advancements in this field.