利用代謝體學揭示農民尿液代謝模式與熱危害暴露之間的相關性

Abstract

隨著全球氣溫持續上升，極端高溫事件變得更加頻繁和嚴重。熱暴露對戶外工作者健康的不利影響成為職業健康問題，特別是在重體力勞動和水分不足的情況下。許多文獻顯示，由於腎臟的易感性，熱壓力可能導致不明原因的慢性腎臟病。與其他職業相比，農民可能更容易受到熱壓力的影響，因為他們從事重體力勞動，體內產生的代謝熱和周圍環境的外部熱量共同作用，導致熱危害的風險增加。 本研究利用基於核磁共振的代謝體學方法研究農民與非農民的尿液代謝體變化。研究對象為在雲林彰化基督教醫院做健康檢查的76位農民和38位非農民，共114人。其中1人沒有提供尿液檢體，共113個尿液樣本。經過圖譜前處理後，排除17個可能影響結果的異常值，包含8個高糖尿異常、8個圖譜品質不佳和1個乳酸過高，最後共96個尿液樣本。接著將人群依照不同因子分類到不同的組別，進行多變量和單變量分析。目的是探討與環境熱壓力相關的關鍵尿液代謝物及其對腎臟可能產生的不良健康影響，並提高我們對高暴露族群熱壓力對代謝影響的了解。 多變量分析結果顯示農民與非農民的尿液代謝物存在顯著差異。單變量分析結果顯示，農民相較於非農民，尿液代謝物的濃度有顯著變化，包括creatinine的降低；taurine和trimethylamine N-oxide (TMAO)的增加。Taurine和TMAO的顯著增加與先前對醫護人員熱暴露下的尿液代謝體研究發現一致。我們的研究指出taurine和TMAO可能和熱暴露具有相關性的可能。在重體力活動的組別也有觀察到類似的代謝變化。因此造成農民與非農民差異的可能原因是從事重體力勞動。另外，根據我們目前的數據，guanidoacetate可能有潛力成為衡量熱暴露的生物標記，因為guanidoacetate的增加與戶外工作時間的增加有相關，減少則是和CKD-EPI相關，顯示guanidoacetate與腎臟傷害可能存在關聯。 這項非標的代謝體學研究發現，暴露熱的農民和沒有暴露熱的非農民之間的尿液代謝模式有顯著差異。這些資訊可能表明潛在的健康影響，並為早期診斷提供分子資訊。另外，我們發現了guanidoacetate可能是潛在的生物標記，它可能與腎損傷之間存在潛在關聯。未來的研究可以更深入地探索guanidoacetate在熱壓力調節的角色。

As global temperatures continue to rise and extreme heat events become more frequent and severe, the adverse health effects of heat stress on outdoor workers have become an occupational health issue, particularly under conditions of physical exertion and inadequate hydration. Previous literatures have revealed that heat stress can cause chronic kidney disease of unknown etiology (CKDu) due to the susceptibility of the kidney. Compared to other occupations, farmers are more susceptible to heat stress. This may be due to their heavy physical labor, which results in a high risk of heat stress caused by the combined effects of metabolic heat generated by the body and external heat from the surrounding environment. Nuclear magnetic resonance (NMR)-based metabolomics was used to investigate urinary metabolites in farmers and non-farmers. The study population were 114 participants with 76 farmers and 38 non-farmers in health examinations at Yunlin Christian Hospital. One participant did not provide a urine sample, a total of 113 urine samples were collected. After spectral processing, 17 outliers that might affect the results were excluded, including 8 with abnormally high glucose levels, 8 with poor spectral quality, and 1 with high lactate levels, resulting in a total of 96 urine samples. The population was then classified into different groups based on various factors, and multivariate and univariate analyses were performed. We examined critical urinary metabolites related to environmental heat stress and their possible adverse health effects on the kidney. The goal is to improve our understanding of the metabolic mechanisms of heat stress in highly exposed populations. The results of multivariate analysis revealed that there were significant differences in urinary metabolites between farmers and non-farmers in the partial least squares discriminant analysis model. In addition, independent t-tests results showed that compared with non-farmers, decreased creatinine level and increased taurine and trimethylamine N-oxide (TMAO) levels were found in the urine of farmers. Increased taurine and TMAO were consistent with previous findings on urinary metabolites in healthcare workers exposed to heat. Our study raised the possibility that taurine and TMAO might be related to heat exposure. In addition, similar metabolic changes were observed in the heavy physical labor group. The possible reason for the difference between farmers and non-farmers might be engaged in heavy physical labor. Additionally, guanidoacetate may have the potential to become a biomarker for measuring heat exposure. This was because an increase in guanidoacetate was correlated with longer outdoor working hours, whereas its decrease was associated with chronic kidney disease epidemiology collaboration (CKD-EPI). This suggests a possible link between guanidoacetate and kidney injury. This untargeted metabolomics study revealed significant differences in urinary metabolic patterns between farmers exposed to heat and non-farmers not exposed to heat. This information might indicate adverse health effects and provide molecular information for early diagnosis. In addition, we found that guanidoacetate may be a potential biomarker association with renal injury. Future studies could further examine the role of guanidoacetate in regulation of heat stress.