幽門桿菌首次感染主要發生在兒童。它確實的傳染途徑仍不確定，但胃口傳染或糞口傳染是最常被接受的二種傳染途徑。大部分被感染的兒童，甚至沒有症狀都變成慢性感染且一直持續到成人。因此推論兒童早期獲得幽門桿菌感染使得他們有造成比較長時間的慢性感染傾向，因此產生較嚴重的不良結果。例如：潰瘍，甚至於癌性病變。診斷兒童幽門桿菌感染最可信賴的非侵入性方法，仍需要大規模的研究證實。此外由於幽門桿菌感染在兒童的病理性影響仍有爭論，因此對於開始治療兒童幽門桿菌的指標，則無法被廣泛的推薦。因此，在我的博士論文裡，基於臨床的評估、體外分子研討、以及體內小鼠模型研究，我嘗試去闡述幽門桿菌感染兒童後，其臨床與病理上的重要性。
我研究的特殊目的包括：一、探討兒童幽門桿菌感染的盛行率、傳染途徑、以及危險因子；二、評估兒童感染的臨床顯著性，以提供未來治療依據的證據；三、闡述路易斯抗原在兒童與成人感染結果上所扮演的不同病理角色；四、在小鼠模型上，確認與幽門桿菌自動根除有關的宿主因素。
第一部分的結果顯示，幽門桿菌的盛行率從兒童早期到成人快速的增加，到30歲以後到達一個水平。接著證明幽門桿菌與A型肝炎盛行率不同，糞口傳染的途徑無法解釋台灣人的幽門桿菌傳染。與幽門桿菌感染且消化不良母親同住的兒童，比未感染幽門桿菌母親的兒童有比較高得到幽門桿菌感染的機會（P值< 0.05）。基於內視鏡檢查的結果，兒童與幽門桿菌相關的潰瘍比率相對的比成人來得小。從社區性的研究發現，大部分幽門桿菌感染的兒童都沒有症狀，但是患有短暫、反覆性上腹痛的學齡兒童（25%）比對照組（9%）有顯著高的幽門桿菌感染率。
我在一個橫向研究中發現小於十歲幽門桿菌感染的兒童比未感染的對照組，有顯著較低的身體質量指數（BMI）和鐵蛋白（Ferritin）。在我的一個介入性研究中發現，無症狀的幽門桿菌感染兒童根除細菌後比未感染的對照組，身高和體重皆有較高的增加淨值。如此的結果與幽門桿菌感染並有十二指腸潰瘍的成人，在根除細菌後有明顯的BMI增加，可以互相印證。
因為兒童與成人在幽門桿菌感染的盛行率有很大的不同，並且基於路易斯抗原在幽門桿菌移生（colonization）上扮演重要的角色，我因此探討是否兒童與成人有不同的路易斯抗原表現，而造成不同的疾病結果。顯然的，幽門桿菌感染的成人比兒童，在胃體部有較高的細菌密度以及路易斯抗原b（Leb）的強度。我的資料建議幽門桿菌感染後表現較高的唾液酸化活性（100  sialyl-Lex/Lex），但不是Leb的兒童，傾向於會產生潰瘍以及嚴重的發炎反應（P值< 0.05）。接著的小鼠體內研究顯示，在早期感染幽門桿菌的小鼠而自動清除者，顯著的與胃較低IL-10以及sialyl-Lex，但與較高IFN-γ表現有相關。
爲了確認一個可幸賴且較經濟，可用來篩檢兒童幽門桿菌感染的非侵襲性診斷工具，我設計了一個低劑量（25毫克）尿素的碳13-尿素吹氣試驗，並確認它可以分別達到89%敏感度與95%特異度，來篩檢兒童的初次感染。我也證實了台灣分離出的高MIC 對metronidazole-抗藥性的幽門桿菌菌株的原因，rdxA比frxA基因突變占了更主要的角色。
總括來說，我的論文證明了台灣兒童幽門桿菌感染的盛行率以及特殊的家庭內傳染情形。除了對於潰瘍性疾病外，也允諾開始兒童幽門桿菌根除治療的條件，尤其對於部分的反覆性腹痛、生長遲滯甚至鐵質缺乏的兒童。也證實了胃中sialyl-Lex表現與IL-10/IFN-γ的反應參予了決定兒童幽門桿菌持續的感染。因此，控制路易斯抗原調控路徑與細胞激素反應的介入，將有希望控制人類的幽門桿菌感染。

Primary H. pylori infection was mainly acquired in children. The exact transmission route of H. pylori remains uncertain, but the gastro-oral or fecal-oral routes are commonly attributed. Most of them become chronically infected until adults, even without symptoms. Therefore, it has been proposed the early acquisition of H. pylori in childhood could be predisposed to a longer chronicity and thus leads into a more adverse consequence as ulceration or even carcinogenesis. The most reliable non-invasive method for the diagnosis of H. pylori in children remains in need of large scaled validation. Moreover, as the pathogenic impacts of H. pylori infection on children remain debating, the indications to start the H. pylori eradication in children have not been widely recommended as yet. Accordingly, in my PhD dissertation, I intended to elucidate the possible clinical and pathogenic significance of H. pylori infection in children based on the clinical assessment, the in vitro molecular approaches, and the in vivo mice model experiments.
The specific aims of my project included 1) to study the prevalence, transmission route, and risk factors of H. pylori infection in children; 2) to assess the potential clinical significance of the childhood infection thus to provide the evidence for therapeutic basis; 3) to elucidate the different pathogenic roles of gastric Lewis antigen on the infection outcomes between children and adults; 4) to identify the host factors associated with the spontaneous eradication of H. pylori in a mice model.
The results for the first-part specific aim showed the prevalence of H. pylori infection was rapidly increased from early childhood to adults and reached a plateau after age of 30 years. Not compatible with the HAV prevalence, the fecal-oral route was further validated to be not responsible to H. pylori transmission in Taiwanese. Children living with H. pylori-infected dyspeptic mothers had a higher risk to get H. pylori infection than those living with non-infected mothers (P<0.05). Based on the results of endoscopy, the rates of H. pylori-related peptic ulcers in children was rather lower than adults. From a community study, I disclosed most H. pylori infected children seem to be asymptomatic, but the schoolchildren with short-term recurrent epigastric pain had a significantly higher rate (25%) of H. pylori infection than control (9%).
A significantly lower body mass index (BMI) and ferritin levels in H. pylori-infected children aged less than 10 years than non-infected controls was found in the cross-sectional study. Based on my intervention trail, a positive net gain of body weight and height in asymptomatic children after H. pylori eradication was disclosed to be higher than those of the non-infected controls. Such a data had compatibility to the H. pylori-infected adults with duodenal ulcers, who could significantly achieve increased BMI after H. pylori eradication.
There was a large difference of the prevalence rates of H. pylori infection between children and adults. Concerning Lewis antigens play important roles for H. pylori colonization, I further elucidate whether different Lewis antigen expressions to link with different disease outcomes between children and adults. Evidently, the H. pylori-infected adults had a higher H. pylori density and intensity of Lewis b (Leb) at corpus than H. pylori-infected children (P<0.05). My data suggested H. pylori-infected children expressed with higher sialylation activity (100 multiply sialyl-Lex/Lex), but not Leb, predispose to the development of peptic ulcers and more severe inflammation (P<0.05). The in vivo mice study further revealed the successful spontaneous clearance of H. pylori in early acquisition age was significant related with the a lower expression of IL-10 and sialyl-Lex, but with a higher expression of IFN-γexpression (P<0.05).
To validate the reliable and economic diagnostic tool in a non-invasive manner for H. pylori survey in children, I studied a low-dosed (25 mg urea) 13C-urea breath test and validated it could be optimal to yield a sensitivity and specificity as 89% and 95% for naïve infection screening, respectively. I also have identified the rdxA rather than frxA gene mutation could play the in-major role to account for the high MICs of metronidazole-resistant H. pylori isolated in Taiwan.
In conclusion, my dissertation demonstrated the prevalence and the specific intra-familial transmission of H. pylori infection in Taiwanese children. It should be promising to start H. pylori eradication for the children, especially for a part of recurrent abdominal pain, growth retardation, and even iron deficiency, besides to the peptic ulcer diseases. The gastric sialyl-Lex expression and IL-10/IFN-γimmune responses should have been involved to determine the persistent infection in children. Accordingly, interventions to control the Lewis antigen–mediated pathway and cytokine responses are thus promising for the control of H. pylori infection.

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