塑膠微粒經腸胃道暴露之健康效應研究

Abstract

塑膠微粒（Microplastics, MPs），是環境中的新興污染物，泛指直徑小於五毫米的塑膠球體、纖維的塑膠碎片。人類暴露塑膠微粒的途徑主要可分為吸入、皮膚接觸和攝入。其中攝入被認為是主要途徑，已有許多研究在自來水、瓶裝水、食鹽等各類食物中檢測到塑膠微粒，顯示人類可能通過食物鏈暴露塑膠微粒，此外，近年來塑膠食品包裝容器也被認為是塑膠微粒的主要來源。

現今已有大量的動物暴露塑膠微粒研究證據，顯示塑膠微粒會引起不良的健康效應，當塑膠微粒經攝入途徑暴露，會經腸胃道屏障吸收進入體內，並可能進一步的分佈在各器官中，如肝臟、腎臟等，甚至可能穿越血腦屏障累積於腦部，導致許多器官的不良健康效應，包含氧化壓力、肝臟脂質代謝異常、醣類代謝異常以及腸道菌群異常等問題，進而可能增加罹患胰島素阻抗、心血管疾病等風險。而同時也已有許多研究於人類生物檢體中檢測到塑膠微粒，如糞便、血液、肝臟、胎盤檢體等，顯示人類同時也暴露在塑膠微粒的風險當中。迄今，塑膠微粒相關的人類研究僅停留在塑膠微粒暴露的評估上，尚未有研究進行塑膠微粒對人體的健康風險評估，因此塑膠微粒對人體的健康風險仍未知。

本研究通過國立臺灣大學行為與社會科學研究倫理委員會審查，符合研究倫理規範，案號202205HM049。招募符合條件的健康受試者，年齡區間在20歲至35歲，並且必須居住在台北和新北市。進行為期一週的研究，收集塑膠使用相關之個人習慣問卷與一週塑膠食品包裝容器紀錄，於研究第七天，於台大公衛學院進行生理指標的量測，包含身高、體重、腰圍與血壓，並收集糞便、血液及尿液檢體。使用µ-FTIR進行糞便中塑膠微粒濃度的檢測，其結果將與食/飲品包裝容器使用量，作為塑膠微粒的暴露指標，同時利用糞便、血液與尿液進行健康效應相關指標的量測，包含血液常規、肝腎功能標誌物、脂質與醣類代謝相關指標、心血管相關指標、腸道菌群、短鏈脂肪酸與代謝體等，探討塑膠微粒暴露對人體健康效應的影響。

本次研究共招募到五十名受試者，平均年齡24歲，共有女性33位與男性17位，教育程度皆大學以上。糞便中塑膠微粒濃度為平均每乾重糞便中有44.16顆的塑膠微粒，五十個樣本中有八個樣本未檢測到塑膠微粒。六天使用的食/飲品包裝容器平均使用量為18個。於脂質與醣類代謝相關指標結果，各分組有較一致且集中的趨勢，在糞便中檢測到塑膠微粒時，>11.5組之HDL 濃度會顯著下降；食/飲品塑膠包裝容器使用量分組下，使用量較高組別的TG、LDL和TCH/HDL顯著上升，HDL顯著下降。糞便中塑膠微粒濃度和Insulin AC呈現正相關；食/飲品塑膠包裝容器使用量、瓶裝水飲用頻率與使用茶包的頻率，皆與HbA1c呈現正相關，發現脂質與醣類代謝與塑膠微粒暴露具有一定相關性外，也與BMI及心血管風險指標fibrinogen趨勢相同，綜合結果顯示塑膠微粒暴露可能導致肥胖、心血管疾病以及胰島素阻抗風險，且與過去部分動物實驗結果趨勢相同，但在肝臟相關指標的結果發現，糞便中的塑膠微粒濃度與肝發炎指摽AST、ALT呈顯著負相關，在已排除慢性肝炎的情況下，推測可能部分塑膠微粒種類可能與肝臟保護作用相關。進一步地利用腸道菌群及短鏈脂肪酸的檢測，了解塑膠微粒暴露造成健康效應之機轉，結果顯示在各分組間有發現部分的菌群與短鍊脂肪酸有顯著差異，但綜合所有組別結果來看，並沒有顯著並一致的變化趨勢。而在血中代謝體分析中，則有數個代謝物與糞便中塑膠微粒濃度有顯著相關，包含與許多脂質及醣類代謝相關的代謝物，如檸檬酸、乙醯肉鹼、苯丙胺酸等，綜合所有代謝物變化之趨勢，發現塑膠微粒暴露可能造成細胞代謝異常，並影響脂質與醣類代謝，導致不良健康效應。

本研究為小規模的人類健康風險評估研究，初步結果發現人類暴露塑膠微粒所造成的健康效應，與動物實驗暴露塑膠微粒的結果相近，塑膠微粒暴露可能導致脂質與醣類代謝的異常，增加肥胖、胰島素抵抗與心血管疾病的風險。但目前在塑膠微粒暴露指標的建立上，仍有許多限制之處，未來需要更進一步且更大規模的研究，才能更了解塑膠微粒對人體健康的影響。

Microplastics (MPs) are generally referred as various plastic products or plastic fragments with a particle size less than 5 mm in diameter. MPs are widely distributed in the environment and have been detected in human placenta, feces and blood. The exposure routes of microplastics include ingestion, inhalation and skin contact. Ingestion is considered the major route of human exposure to MPs. Recently, animal studies have shown that MPs administered through the gastrointestinal tract may be absorbed and cause liver and kidney injuries. Studies also find that MPs cause alteration in lipid and glucose metabolism and gut microbiota dysbiosis. However, it remains unknown whether MPs could cause any toxicities in humans. Here, we conducted a cross-sectional study to investigate if MPs exposure are associated with adverse health outcome.

The study was approved by the Research Ethics Committee of National Taiwan University (No. 202205HM049). Young adults were recruited from the metropolitan Taipei area. A dietary questionnaire for 6 days and plastic usage habits associated with MPs exposure over the past three months. Fecal samples, peripheral blood and urine were also collected. Fecal samples were prepared and examined under micro-FTIR to determine the presence of MPs. Urinalysis and CBC were performed. Plasma biochemistry for liver and kidney injury was also tested. To examine the homeostasis of lipids and glucose, lipid profile and marker for glucose metabolism were determined. Further, 16S rRNA gene sequencing Short-chain fatty acid relative quantitation was conducted from the fecal samples to determine the composition of gut microbiota and SCFAs composition. LC-MS untargeted profiling from plasma to determine metabolite changing.

A total of 50 adults with an average age of 24, females of 33 and male of 17 were included in the analysis. The mean concentration of fecal MPs was 44.16 per gram of fecal dry weight. The average plastic packaging container usage of 6 days was 18. Grouping by the concentration of fecal MPs, plastic packaging container usage of 6 days, and four plastic usage habits. The habits include the material of commonly used bottles, frequency of bottled water consumption, tea bag usage frequency, and straw-biting behavior. The Multiple regression analysis results showed HDL level was significantly lower in the >11.5 group as compared to the Undetectable group, and also significantly lower in the usage of container >18 as compared to the group of ≤18. The TG, LDL and TCH/HDL levels were significantly higher in the usage of container >18 as compared to the group of ≤18. In glucose metabolism markers, insulin level was positively correlated with the concentration of fecal MPs. The HbA1c levels were positively correlated with the average plastic packaging container usage, the frequency of bottled water consumption, and the tea bag usage frequency. In this study, we found significant differences between groups in HDL and insulin levels, which were consistent across all grouping methods. Further, the BMI and fibrinogen levels were significantly higher in the usage of container >18 as compared to the group of ≤18. To explore the MPs' toxicological mechanism, we conducted the gut microbiota, SCFAs, and metabolite profiling. However, the results of gut microbiota and SCFAs weren’t found to correlate across all grouping methods. In the metabolites results, we found several metabolites were significantly related to lipid and glucose metabolism, such as Hypoxanthine, Phenylalanine, Paraxanthine, and citric acid. It was found that exposure to MPs may cause abnormal cellular metabolism and affect lipid and carbohydrate metabolism, leading to health effects.

Our pilot study suggests that MPs exposure may cause metabolic disturbances and affect lipid and glucose homeostasis. Moreover, the results are consistent with the previous finding from animal studies. Therefore, increasing the risk of obesity, insulin resistance, and cardiovascular disease. Further study with more subjects is needed to confirm the findings.