抑制dusp6 (Dual-specificity phosphatase 6) 發現”減肥益生菌” ?!!

吃不胖不是夢 國衛院發現抗肥菌株 2016-12-13 〔記者林惠琴／台北報導〕打擊肥胖有新發現！國家衛生研究院昨發表最新研究，抑制「雙特異性去磷酸酶」（dusp6）基因，有利於改變腸道環境，達到調控菌相平衡，就有機會遠離肥胖，研究更已初步發現抑制dusp6基因後、腸道會產生可「抗肥胖」的特定菌株，目前正在篩選測試中，預計最快兩、三年內可據以開發成益生菌之類的保健食品，讓民眾方便服用，輕鬆抗肥、保持窈窕身材。人類吃高油脂食物會發胖的原理，除了食物熱量，擾亂腸道菌相造成發炎、影響代謝機能，也是肥胖重要成因，人體的腸道菌相平衡更與肥胖代謝、自體免疫、癌症等疾病有關。國衛院二○一二年起，積極研究如何利用調整腸道菌相來治療或控制發炎性疾病與肥胖代謝疾病。 國衛院免疫醫學研究中心助研究員高承源的團隊，歷時四年研究發現，人類、老鼠及許多動物體內都有種「雙特異性去磷酸酶」（dusp6）基因，而剔除dusp6基因的小鼠，就算餵食高油脂飼料，卻仍能維持腸道菌相平衡，減少細菌內毒素滲漏至血液循環引起發炎，達到抑制肥胖效果。 研究團隊進一步經糞菌移植方式，將dusp6基因剔除小鼠與野生小鼠的腸道菌相分別移植到無菌鼠上，再餵食相同高油脂飼料，結果十六週後，前者小鼠較後者增加十五％的能量消耗，並減輕約二十％體重、體脂肪。

最快兩年 開發成益生菌 研究人員阮振維說，研究團隊利用RNA定序分析基因剔除小鼠的小腸轉錄體，發現dusp6基因缺失會提高腸道上皮細胞緊密度，維持腸黏膜與腸道菌相的平衡；高承源補充，研究也初步發現抑制dusp6基因後、腸道會產生可「抗肥胖」的特定菌株，維持有利代謝的腸道菌相，目前正在嘗試找出影響的菌株，只要經確認就可藉以開發出有助於打擊肥胖、改善代謝的益生菌之類保健食品，讓民眾方便服用。 國衛院研究已刊登於國際期刊《自然微生物》（Nature Microbiology）。如果研究順利，最快兩、三年就能研發出有助減肥的益生菌，定期食用能穩定腸道內菌叢生態，減少肥胖及相關代謝疾病。

Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice  Nature Microbiology 2, Article number: 16220 (2016) The gut microbiota plays profound roles in host metabolism and the inflammatory response associated with the development of obesity. Dusp6-deficient mice have been shown to be resistant to diet-induced obesity, but the mechanism behind this remains unclear. 16S ribosomal RNA gene analysis demonstrated that dusp6-deficient mice harbour unique gut microbiota with resistance to diet-induced-obesity-mediated alteration of the gut microbiome. Using a germ-free mouse model, we found that faecal/gut microbiota derived from dusp6-deficient mice significantly increased energy expenditure and reduced weight gain in recipient wild-type mice fed on a high-fat diet. On analysis of the intestinal transcriptome of dusp6-deficient mice, we found that dusp6 deficiency mainly induced biological processes involved in metabolism and the extracellular matrix, particularly the peroxisome proliferator-activated receptor gamma (Pparγ) pathway and tight-junction genes. Furthermore, dusp6-deficient mice have a high-fat-diet-specific transcriptomic response to reverse the expression of genes associated with intestinal barrier functions and mucosal immunity involved in microbiome homeostasis. This study demonstrates that dusp6 deficiency is a strong genetic factor shaping gut microbiota, and that it confers obesity protection by ameliorating the gut microbiota response to diet-mediated stress.