空氣汙染對人體的健康危害影響距甚，研究指出多種重大疾病和空氣污染有密切的相關，例如呼吸道與肺部疾病、心血管疾病以及糖尿病等。而空氣污染中的細懸浮微粒 (Particulate Matter, PM)，更容易直達胸腔，並增加各種心血管疾病和提高死亡率的風險，台灣測到的懸浮微粒濃度顯示空氣汙染議題十分重要並須解決。PM會經由鼻粘膜纖毛輸送系統從肺部進入人體腸道，因此PM也被認為可能會影響腸胃道疾病的發生，特別是發炎性腸道疾病。流行病學的研究發現，長期暴露於較高濃度的二氧化氮和PM與早發性克隆氏症的風險增加有關。此外，PM總測量的增加與發炎性腸道疾病住院風險增加有關。另外，短期暴露PM的臭氧可能與某些闌尾炎的病例可能有相關。然而PM的流行病學研究仍然有限制的因素需要考慮，例如監測站測量到的空氣汙染數值可能與個人實際暴露到的量有所差異。因此除了流行病學的證據之外，需要更多生物的研究以釐清PM與發炎性腸道疾病的關係與疾病機轉。以動物模式的研究發現PM10造成小鼠的腸道發炎並影響到腸道微生物群的平衡。然而空氣汙染中的PM成分複雜，極易吸附多環芳香烴碳氫化合物 (polycyclic aromatic hydrocarbons, PAHs)等有機污染物、重金屬以及大氣中細菌的細胞壁內毒素，PM中的多環芳烴PAHs會活化AhRpathway，AhR是PAHs的接受體，會參與調控體內對於環境污染物以及內生性芳香碳氫化合物的代謝作用，可以針對環境外來物啟動去毒的機制反應。PM中的細菌內毒素已知會引起發炎反應，然而近幾年許多研究指出AhR還會影響免疫細胞的活化以及細胞激素 (cytokine) 的表現，因此AhR也認為可以調控發炎的反應。而調控發炎反應的NF-kB 也被發現可以參與AhR的訊息路徑，顯示NF-kB 與AhR可能具有cross-talk的效應共同影響發炎反應。在腸炎的動物模式中發現AhR可以調控發炎反應，同時在克隆氏症病人腸道上皮細胞的AhR表現明顯增加，其AhR下游的CYP1A1與IL-8也受到AhR調控而增加表現。目前的研究仍尚未釐清PM中PAHs與細菌內毒素引起發炎性腸道疾病的毒性分子機制。唯有隨著更多的生物學研究的進行，才會更加清楚瞭解PM空氣污染物對胃腸功能影響的作用機制。因此，本研究計畫探討胃腸道炎症在PM引起的健康效應中應是值得研究與重視的議題。 ;Air pollution can have a serious impact on human health. There are a number of major diseases closely related to air pollution such as respiratory and lung diseases, cardiovascular diseases and diabetes. Particulate matter (PM) in air pollution is more easily delivered to the thorax and increases the risk of various cardiovascular diseases and increases the mortality rate. The aerosol concentration detected in various emission sources showed the importance of air pollution issues in Taiwan. PM enter into the human gut from the lungs via the mucociliary transport system, which is also considered to affect the occurrence of inflammatory bowel disease (IBD). Epidemiological study reported that long-term exposure to higher concentrations of nitrogen dioxide and PM were associated with an increased risk of early-onset Crohn's disease. In addition, a rise in total measured air pollutants was associated with an increased risk of hospitalization for inflammatory bowel disease. Several studies demonstrated an association between ozone exposure and appendicitis. However, important limitations of epidemiologic air pollution studies should be considered. A majority of limitations were air pollution exposures generally based on regional estimates, not personal monitoring. Also, gastrointestinal diseases were identified based on administrative databases that may contain misclassification errors. Animal study showed that PM10 trigger mice intestinal inflammatory responses and alter gut microbiota populations. The PM components in air pollution are complex and PM easily adsorb organic pollutants such as polycyclic aromatic hydrocarbons (PAHs), heavy metals and endotoxins in the air by microorganisms. PAHs activate aryl hydrocarbon receptor (AhR) pathway, which regulated the metabolism of environmental pollutants and endogenous aromatic hydrocarbons, and initiated a detoxification mechanism response to environmental alien substances. Bacterial endotoxins are lipopolysaccharide (LPS) from cell wall components of the outer membrane of gram‐negative bacteria, which are an important biological component of PM and have adverse effects on human health. It is well known that endotoxin exhibit inflammatory effects. The activation of NF-kB involved AhR expression and AhR-regulated genes, which indicated cross-talk effects between AhR and inflammatory responses. It was reported that AhR expression levels were increasing and the CYP1A1 and IL-8 also upregulated in colonic epithelial cells from Crohn's disease patients. However, the toxicological mechanisms of PM-induced inflammatory bowel disease is still unclear. As more biological studies performed, the clearer picture of the effects of PM air pollutants on gastrointestinal function is bound to emerge. Thus, gastrointestinal inflammation is also a worth investigating issue in PM-induced health effects.
