近年來眾多文獻指出國人罹患過敏性氣喘人口有逐漸增加的趨勢，如何改善過敏性氣喘症狀將是未來重要課題之一。益生菌原為腸道有益菌叢，因其對於人體有調節免疫能力、抵抗外來病原菌侵入，以及維持腸道內菌叢生長等等多重保護效果，故日漸廣泛應用於健康食品使用，但不同種類的益生菌具有不同功能，本研究主要在過敏性氣喘小鼠動物模式中探討L. gasseri PM-A0005是否可改善小鼠發炎反應，以及給予小鼠不同劑量L. gasseri PM-A0005是否會有不同功效，從小鼠肺功能、肺泡沖洗液所分泌細胞激素、抗原專一性抗體、組織切片分析結果得知L. gasseri PM-A0005可藉由抑制TH1、TH2細胞激素及改變抗原專一性抗體的分泌來減緩小鼠的發炎反應。為調查不同劑量L. gasseri PM-A0005是否會影響小鼠基因變化，便利用RNA微矩陣基因晶片分析小鼠肺部周邊淋巴結和腸繫黏膜淋巴結基因變化，發現過敏性氣喘小鼠食用L. gasseri PM-A0005則會促使與脂肪代謝相關基因表現量增加。從其中挑選出具有潛力基因”過氧化物酶體增殖激活受體”(Peroxisome proliferator-activated receptor γ，PPARγ )，PPARγ為核內荷爾蒙受體成員之一，可調控脂肪代謝，最近研究發現PPARγ也具有抗發炎功能。給予過敏性氣喘小鼠PPARγ促進劑Rosiglitazone，發現Rosiglitazone可抑制TH2細胞激素分泌來改善小鼠肺部發炎。最後利用PPARγ 一半表現量的PPAR-γ P456L突變鼠給與塵蟎致敏，發現此小鼠比野生型(wild type)小鼠發炎情形來的嚴重。若多給予PPARγ 一半表現量的PPAR-γ P456L突變鼠L. gasseri PM-A0005則可改善其發炎情形，但改善程度卻不及野生型小鼠。綜合本實驗結果，L. gasseri PM-A0005經由PPARγ的途徑改善了塵蟎所引起小鼠的過敏反應。

Probiotics are normal inhabitants in the gastrointestinal tracts of man and are widely considered to exert a number of beneficial roles including immunomodulation, interference with enteric pathogens, and maintenance of a healthy intestinal microflora. In recent years, studies of probiotics have also confirmed their extra-intestinal effects, particularly for the prevention of allergic diseases. However, the anti-allergy mechanism of probiotics is still unclear. In the first part of this study, we found that continuous feeding of Lactobacillus gasseri (L. gasseri) PM-A0005 107 CFU/200 ml or 109 CFU/200 ml for 4 weeks in Der p-sensitized and challenged mice could prevent allergen-induced airway inflammation. There were also significant changes of airway hypersensitivity, TH1 and TH2 cytokine patterns, lymphocyte proliferations and immunoglobulin production between L. gasseri PM-A0005-treated and non-treated mice. In the second part of study, we applied microarray analysis of the lung draining lymph nodes and mesenteric lymph node of mice to detect genes expression signal pathways and genetic profiling of immunological tolerance induced by L. gasseri PM-A0005 that plays an essential role of in the prevention and therapeutic effects on allergic asthma. We found that there was significantly decrease of inflammatory and chemokines genes expression and increased of carbohydrate and lipid metabolism genes expression in the L. gasseri PM-A0005-treated mice as compared to non-treated sensitized and challenged mice. Thirdly, we have picked up one candidate targeted gene, PPARγ (peroxisome proliferator-activated receptor γ), to study the beneficial effect of probiotics on the allergic induced airway inflammation. Previously, it has been reported that PPARγis a member of the nuclear hormone receptor family that not only is prominently involved in adipogenesis and metabolic regulation but also exerts pleiotropic anti-inflammatory effects in the lung, we hypothesized that PPARγ may play an important role in allergen-induced airway inflammation. The allergen-sensitized effect on murine model of asthma was applied in PPAR-γ P456L mutant mice by evaluating AHR, total numbers of inflammatory cells and cytokines secretion in bronchoalveolar fluid (BALF), and lung inflammation after mite allergen sensitization and challenge. Moreover, probiotics treatments PPAR-γ P456L mutant mice and wide type mice were administrated in allergen-sensitized mice. In summary, our results showed that PPAR-γ play important role in the inhibitory effect of allergen-induced airway inflammation in mice. And the anti-allergic effect on L. gasseri PM-A0005 may through activation of PPARγ to alleviate airway inflammation in allergen-sensitized murine model of asthma.

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