吕农华+吕宾+张振玉等：双歧杆菌四联活菌片可有益于Hp根除治疗

Frontiers in Immunology[IF:8.786]

① 开展一项为期2.8年的多中心、随机、双盲、安慰剂对照试验，分为益生菌（n=140）或安慰剂组（n=136）；

② 两组患者均接受14天含铋剂四联疗法，同时联合双歧杆菌四联活菌片或安慰剂，干预4周，治疗前后收集唾液、胃粘膜和粪便样本，进行16S测序；

③ 双歧杆菌四联活菌片组胃肠道不良反应发生率显著低于安慰剂组；

④ 根除Hp后肠菌结构显著改变，补充四联活菌片可改善药物带来的拟杆菌门丰度降低，促使菌群波动更平稳，抑制口腔致病菌生长。

Probiotics modulate gastrointestinal microbiota after Helicobacter pylori eradication: A multicenter randomized double-blind placebo-controlled trial
11-08, doi: 10.3389/fimmu.2022.1033063

【主编评语】幽门螺杆菌（Hp）是全球感染传播最广泛的细菌之一，会导致慢性胃炎，并增加消化性溃疡、胃癌和黏膜相关淋巴组织淋巴瘤的患病风险。目前，含铋剂的四联疗法已成为国际范围内认可的Hp治疗一线用药方案，但会导致患者胃肠道不良反应及肠道菌群的短期紊乱。近日，南昌大学第一附属医院吕农华、浙江中医药大学第一附属医院吕宾、南京市第一医院张振玉作为共同通讯作者，南昌大学第一附属医院祝荫等作为共同第一作者，在Frontiers in Immunology发表最新研究，招募了276名Hp患者随机分为益生菌或安慰剂组，两组患者均接受14天含铋剂四联疗法，同时联合双歧杆菌四联活菌片或安慰剂干预4周，发现双歧杆菌四联活菌片干预可降低胃肠道不良反应的发生率，改善胃肠道不良反应和菌群紊乱。总之，干研究为Hp治疗方案的优化以及副作用的减轻提供了新的临床应用方向和思路。

Probiotics modulate gastrointestinal microbiota after Helicobacter pylori eradication: A multicenter randomized double-blind placebo-controlled trial

益生菌可调节幽门螺杆菌根除后的胃肠道微生物群：一项多中心的随机双盲安慰剂对照试验

10.3389/fimmu.2022.1033063

11-08, Article

Abstract:
Background:: Helicobacter pylori (H. pylori) eradication has been reported to cause short-term disruption of gut microbiota. It is acknowledged that probiotics supplementation mitigates side effects induced by H. pylori eradication, yet its role on alleviating dysbiosis of microbiota is obscure.
Objectives:: To evaluate the impact of probiotics on gastrointestinal microbiota after eradication therapy.
Methods: : This was a multicenter, double-blinded, randomized trial done at seven centers in China. A total of 276 treatment-naïve H. pylori-positive patients were randomly assigned to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, furazolidone) combined with probiotics (Bifidobacterium Tetragenous viable Bacteria Tablets) (n=140) or placebo (n=136) for 28 days. Saliva, gastric mucosa and fecal samples were collected before and after therapy for 16S rRNA gene sequencing.
Results: : The incidence of gastrointestinal adverse events was lower in probiotics group compared to placebo group (23.6% vs 37.7%, p=0.016), while there was no significant difference in eradication rate. We found dramatic perturbations of gut microbiota immediately following eradication, with the predominance of Proteobacteria in replacement of commensal Firmicutes and Bacteroidetes, and gradually restored after two weeks. The reduction of gut Bacteroidetes caused by eradication drugs was neutralized with probiotics supplementation. The gastric microbiota was completely reconstituted with H. pylori depleted and other taxa flourished. Of note, patients treated with probiotics showed smaller fluctuations of gastric microbiota compared to those with placebo. We also observed changes of saliva microbiota after H. pylori eradication, illustrated by the overgrowth of Neisseria and depletion of Streptococcus. The expansion of some pathogenic genera, including Porphyromonas, Leptotrichia, in the mouth was suppressed by probiotics.
Conclusion: : This study not only demonstrated the beneficial effect of probiotics implementation on side events during H. pylori eradication but also provided a comprehensive profile of microbiome alterations along gastrointestinal tract that modulated by probiotics.

First Authors:
Cong He,Yong Xie,Yin Zhu

Correspondence Authors:
Zhenyu Zhang,Bin Lyu,Nonghua Lu

All Authors:
Cong He,Yong Xie,Yin Zhu,Kun Zhuang,Lijuan Huo,Yong Yu,Qiang Guo,Xu Shu,Zhijuan Xiong,Zhenyu Zhang,Bin Lyu,Nonghua Lu