2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647153摘要：背景：腸道上皮黏膜除了負責營養吸收，也擔任身體腸道內第一線防禦的重責大任。腸道內已知有許多約1012腸內菌共生，大部分在大腸，少部分則在末端回腸。腸道上皮細胞間藉由緊密結合(tight junction)蛋白複合體以及其他細胞間結合蛋白的接合而構成一腸道與身體組織內部的天然屏障。如果此屏障因故受到傷害，造成腸道通透性的改變，就有可能讓腸道內本來無法進入身體組織內的有害物質如內毒素或是細菌轉移進入組織內或血液中散佈全身，因而對人體健康造成傷害。小腸疾病在過去因不易診斷向來被視為消化醫學的盲區，但隨著新近問世的氣囊輔助性小腸鏡的逐漸普及，可以透過小腸鏡外套管前端的可漲縮性氣囊將柔軟屈區的小腸固定並縮短藉此達到深部插入小腸檢查的目的。然而，氣囊的反覆漲縮對腸道黏膜卻有可能造成腸道黏膜的刺激，同時腸道的縮短堆擠也可能對腸道屏障功能有所影響。根據我們在台大醫院執行氣囊輔助性小腸鏡的先期經驗（台灣少數幾家檢查先驅醫院之一），我們曾觀察到氣囊輔助性小腸鏡檢查後高燒感染的患者，文獻上也已見到英國醫師發表氣囊輔助性小腸鏡檢查後Streptococcus milleri菌血症的病例報告。這些案例提示臨床醫師需注意氣囊輔助性小腸鏡檢查前後腸道屏障功能、通透性功能缺損可能會增加細菌轉移的風險，但相關研究目前文獻上卻付之闕如，這在全世界氣囊輔助性小腸鏡正熱烈發展的當下是相當重要且新穎的研究課題。目的與方法：我們將結合基礎與臨床醫學研究，一方面前瞻性的觀察臨床上小腸鏡檢查前後腸道屏障通透性的變化與腸內菌內毒素血症、菌血症、腸內細菌DNA散播到受檢者血液循環及宿主免疫細胞激素活化的情形。並將探討經口端上消化道的氣囊輔助性小腸檢查（腸內菌較少的腸段）與經肛門端下消化道的氣囊輔助性小腸檢查（腸內菌較多的腸段）是否後者有較高的細菌轉移風險。重要性：本研究將釐清此一新穎的氣囊輔助性小腸鏡檢查對於腸道屏障功能缺損的影響以及從細菌的DNA、內毒素到培養出並辨識菌株，試圖釐清此一腸道菌株轉移問題之重要性，配合患者本身的因素來解釋之，以便提供臨床醫師合乎科學驗證的預防性抗生素治療準則建議，例如是否經肛門端或特殊體弱患者族群應一律採用預防性抗生素等等，俾便造福病患健康。<br> Abstract: The intestinal epithelia serve as the first-line defense against intraluminal bacteria. There are at least 1012 commensal bacteria in the human gut, mostly in the large intestines, some in the terminal ileum. The intestinal epithelia constitute a physical barrier by forming intercellular tight junctions, adherent junctions and other intercellular adherence molecules. If the barrier function is breached due to various stimuli, hazardous luminal bacteria will translocate into ought-to-be-sterile body compartments. The overall results would be detrimental to the human health.The newly developed balloon-assisted enteroscopy systems allow insertion of the enteroscopy deeply into the small intestines by fixation of the soft, redundant small intestines with an inflatable balloon over the tip of the overtube. However, the inflation of balloon might stimulate the intestinal mucosa, and the deep manipulation of intestinal segments might also compromise the intestinal barrier function. According to our preliminary experience of balloon-assisted enteroscopy (which is among pioneer hospitals in Taiwan), we experienced significant cases of suspected post-procedural bacteremia. Besides, there is also a published case report from the UK reporting Streptococcus milleri bacteremia which is caused by bacterial translocation after balloon-assisted enteroscopy. However, currently there is neither clear guideline nor original study focusing on the intestinal barrier, permeability defects or bacterial translocation. This is an important, timely and novel research topic in the current rapidly developing era of balloon-assisted enteroscopy.AIM: To investigate the impact of balloon-assisted enteroscopy on the intestinal barrier, permeability defects, recovery and risk of bacterial translocation by a clinical prospective observational study.We will combine both basic and clinical medical research. We plan to conduct a prospective observational study on the alterations of intestinal barrier, permeability defects, endotoxemia, bacterial DNA, cytokine profiles during the peri-procedural period. We will also test the hypothesis that anal approach might be associated with higher risk of bacterial translocation than oral approach, since in the anal approach, the enteroscopy systems would have to traverse through high bacteria content colonic segments.SIGNIFICANCE: The importance of our timely research proposal is that it would elucidate the impact of balloon-assisted enteroscopy on the intestinal barrier/permeability defects and bacterial translocation. Moreover, this research will also address the underlying molecular mechanisms. The ultimate goal is to provide a scientific basis for practical recommendations to improve patients’ health.