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兒童疾病與腸道菌叢

Gut Microbiota and Pediatric Diseases

摘要


成人腸道中含有各種共生菌,每公克糞便約有1014細菌。胎兒在子宮內每天吞進的是無菌羊水,因此它的腸道是無菌的狀態。有趣的是剛出生嬰兒如何獲得其菌叢?而其腸道菌又如何轉變成像大人一樣的型態?嬰幼兒腸道菌種、數量的演進與很多因素有關,例如生產方式、餵食方式、住院設置或母親健康狀況、種族、以及生活環境。傳統研究腸內菌是靠培養法,其敏感度有很大的變異性,完全決定於培養方式(如培養液的選擇)與環境因素。較新的研究方法是以DNA為基礎,針對細菌共有的16S rDNA序列,探測其為何種細菌。透過PCR擴增整個細菌群落的16S rDNA,時間溫度梯度凝膠電泳(temporal temperature gradient gel electrophoresis, TTGE)可按著用以分析PCR所擴增的複雜細菌群落。此方法可排除培養法的培養液偏好缺點,且可提升腸內菌偵測、鑑別與定量的準確性。目前的資料顯示,由新生兒到三歲之間與成人腸道菌叢存在著相當差異,三歲以後的菌叢型態已經接近成人。腸道是人體最大的免疫器官。它接受無數的細菌從口腔中隨著食物進入,有些細菌會被排出、有些則被腸道細胞所認識而產生耐受性。細菌如何與腸道免疫器官互動以調節全身免疫反應?這是當前難解但卻是非常重要的問題。事實上除了年齡的因素外,疾病狀態與健康狀態之菌叢亦頗有不同,克隆氏症及肥胖都是很好的例子。不過,目前使用TTGE分析腸道菌叢的方法仍有其限制,對於細菌在人體內提供的種種代謝途徑,並無法藉此方法了解,而這一部分的腸道菌叢功能與疾病的產生及正常生理功能的維持其實息息相關。事實上目前已漸漸發現,不同菌種可以產生相同的生理或病理作用,所以即使因為種族或環境不同,有不同的菌株,但是人類大體生理功能是一致的。未來希望藉由與腸道菌叢分析資料的對應,可以知道嬰幼兒腸內菌的建立與各種情境之關係;亦可藉以了解嬰幼兒發生疾病時,其腸內菌在疾病前、中、後之型態改變。甚至有望經由腸內菌的調節來預防或治療疾病的發生。

並列摘要


It is interesting to know how the newborns and infants acquire and evolute gut microbiota. The origin of the bacteria colonizing the neonatal gastrointestinal tract is supposed to be affected by mode of delivery, feeding and maternal condition. To identify the individual bacteria, Temporal Temperature Gradient Gel Electrophoresis and clone-based sequencing of 16S rDNA amplicons replaced the conventional culture-based method to perform a more extensive exploration of the gut microbiota. The neonated may acquire phylum Proteobacteria initially, then rapidly followed by Actinobacteria, Bacteroidetes, and Firmicutes. These were the major bacteria patterns in infancy. The infants' gut microbiota pattern will gradually transit into the adult pattern at about the age of three, at what time the food intake of the children is similar to that of the adults. The current literature supports the idea that the gut microbiota signature acquired in infancy may predict or incline to the future development of diseases, for example, allergic diseases or metabolic diseases. Actually, people are more focusing on the functions of these gut microbiota. Although people in different geographic area may display different gut microbiota patterns, their gut microbiota may share the approximate functions. With the advent of next generation sequencing technology, a long-term prospective monitoring on the development of diseases and the evolution of gut microbiota will be very helpful to unravel their causal relationship. The gut microbiota may become the therapeutic target to manipulate.

參考文獻


1. O'Hara AM, Shanahan F: The gut flora as a forgotten organ. EMBO Rep 2006;7:688-93.
2. Rouge C, Goldenberg O, Ferraris L, et al: Investigation of the intestinal microbiota in preterm infants using different methods. Anaerobe 2010;16: 362-70.
3. Vanhoutte T, Huys G, Brandt E, et al: Temporal stability analysis of the microbiota in human faeces by denaturing gradient gel electrophoresis using universal primers and group-specific 16S rRNA gene primers. FEMS Microbiol Ecol 2004;48:437-46.
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5. Vael C, Desager K: The importance of the development of the intestinal microbiota in infancy. Curr Opin Pediatr 2009;21:794-800.

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