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中国儿童幽门螺杆菌根除三联疗法、序贯疗法、铋四联疗法和伴同疗法后肠道微生物群的长期变化。

Long-term changes in the gut microbiota after triple therapy, sequential therapy, bismuth quadruple therapy and concomitant therapy for Helicobacter pylori eradication in Chinese children.

机构信息

Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

出版信息

Helicobacter. 2021 Aug;26(4):e12809. doi: 10.1111/hel.12809. Epub 2021 Apr 25.

DOI:10.1111/hel.12809
PMID:33899288
Abstract

BACKGROUND

We previously reported that the administration of 14-day standard triple therapy (TT), sequential therapy (ST), bismuth-based quadruple therapy (BT), and concomitant therapy (CT) as the first-line therapy for Helicobacter pylori infection in Chinese children achieved eradication rates of 74.1%, 69.5%, 89.8%, and 84.6%, respectively. In this follow-up study, we further evaluated the short- and long-term effects of the four regimens on the gut microbiota in these children.

METHODS

We prospectively recruited treatment-naïve children with H. pylori infection. Fecal samples were collected at week 0, 2, 6, and 52, and alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing.

RESULTS

Sixty-three patients participated in this study (16 with TT, 15 with ST, 16 with BT and 16 with CT). At week 2, the alpha diversity (Shannon and Chao 1 index) was significantly reduced in the TT (p = 0.008, p < 0.001), ST (p < 0.001, p < 0.001), BT (p < 0.001, p < 0.001) and CT groups (p < 0.001, p < 0.001). Some changes persisted in the ST, BT, and CT groups at week 6, and all were restored (expect p = 0.02 with Chao 1 index in the CT group) at week 52. The beta diversity was significantly changed in the BT (p = 0.001) and CT groups (p = 0.001) 2 weeks post-eradication and restored 1 year after therapy. Immediately after therapy, the relative abundance of Proteobacteria was strikingly increased in the ST (p = 0.005), BT (p < 0.001) and CT groups (p < 0.001), and the genus-level analysis showed that the abundances of 23.1%, 43.3%, 78.6%, and 78% of the bacterial genera in the TT, ST, BT, and CT groups were significantly changed. All these changes returned to almost the pre-eradication level 1 year post-eradication.

CONCLUSION

Eradication of H. pylori infection can lead to transient dysbiosis of gut microbiota, and these changes almost recovered 1 year post-eradication, which indicates the long-term safety of H. pylori therapy.

摘要

背景

我们之前报道过,14 天标准三联疗法(TT)、序贯疗法(ST)、铋四联疗法(BT)和伴随疗法(CT)作为中国儿童幽门螺杆菌感染的一线治疗,其根除率分别为 74.1%、69.5%、89.8%和 84.6%。在这项随访研究中,我们进一步评估了这四种方案对儿童肠道微生物群的短期和长期影响。

方法

我们前瞻性招募了未经治疗的幽门螺杆菌感染儿童。在第 0、2、6 和 52 周收集粪便样本,并通过 16S rRNA 基因测序分析肠道微生物群的变化。

结果

63 名患者参与了这项研究(TT 组 16 例,ST 组 15 例,BT 组 16 例,CT 组 16 例)。第 2 周时,TT(p=0.008,p<0.001)、ST(p<0.001,p<0.001)、BT(p<0.001,p<0.001)和 CT(p<0.001,p<0.001)组的 alpha 多样性(Shannon 和 Chao 1 指数)均显著降低。第 6 周时,ST、BT 和 CT 组的一些变化持续存在,第 52 周时均恢复(CT 组 Chao 1 指数除外,p=0.02)。BT(p=0.001)和 CT 组(p=0.001)在根除后 2 周时 beta 多样性显著改变,1 年后恢复。治疗后立即,ST(p=0.005)、BT(p<0.001)和 CT(p<0.001)组的变形菌门相对丰度显著增加,属水平分析显示 TT、ST、BT 和 CT 组中 23.1%、43.3%、78.6%和 78%的细菌属丰度发生显著变化。所有这些变化在根除后 1 年几乎恢复到根除前水平。

结论

幽门螺杆菌感染的根除会导致肠道微生物群的短暂失调,这些变化在根除后 1 年几乎恢复,这表明幽门螺杆菌治疗具有长期安全性。

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