The Impact of Probiotics Supplementation on Gut Microbiota after <i>Helicobacter pylori </i>Eradication: A Multicenter, Open-Label, Randomised Trial

Abstract

Background: Helicobacter pylori (H. pylori) eradication therapy may lead to the perturbation of gut microbiota. The role of probiotics in gut microbiota during eradication therapy is still debated. Design: This was a multicentre, open-label, randomised trial done at seven hospitals in China. 162 patients were enrolled, 79 patients were randomly divided into group A (bismuth quadruple therapy), and 83 patients were randomly subjected into group B (bismuth quadruple therapy supplemented with Medilac-S). Faecal samples were collected before treatment and 2 weeks, 4 weeks, 6 weeks, and 8 weeks after eradication therapy. Gut microbiota was analyzed by 16S rRNA high-throughput sequencing. This trial is complete and registered with Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900022116). Results: The eradication rates of group A and group B were 82.43% and 87.01%, respectively (P>0.05). Compared with baseline, alpha and beta diversity was significantly altered 2 weeks after eradication in both group A and group B, which was restored at week 8. There were no significant differences in alpha and beta diversity between the two groups. Bismuth quadruple therapy resulted in enrichment of some detrimental bacteria taxa such as Klebsiella and Streptococcus that were not recovered by week 8. Probiotics supplementation could rapidly restore the taxa levels of Klebsiella and Streptococcus by week 4 after eradication, and increase the beneficial taxa of Bacillus and Lactobacillales. Functional analysis revealed that lipopolysaccharide biosynthesis and polymyxin resistance pathways were significantly enriched after eradication therapy, while probiotics supplementation mainly enriched the cofactors and vitamins metabolism pathways. Several detrimental taxa were identified to be correlated with features of older age, alcohol use and high BMI, while probiotics supplementation could effectively restore the adverse impact in patients with these characteristics. Conclusion: Probiotics supplementation is beneficial for patients during H. pylori eradication, especially for patients with older age, alcohol drinking, and obesity, which might obtain the maximum benefits. This multicenter, open-label, randomized clinical trial was performed at seven hospitals in China from March 2019 to November 2019. Inclusion criteria: patients aged between 18 and 60 years, at least two positive tests of rapid urease test and 13 C-urea breath test (13 C-UBT). Patients with any one of the following criteria were excluded from the study: history of gastrectomy, previous eradication therapy for H. pylori, peptic ulcer or other upper gastrointestinal lesions, gastrointestinal malignant tumor, contraindication or previous allergic reactions to the study drugs, severe concurrent diseases or malignancy, pregnant or lactating women, the use of antiacids or gastric mucosal protective drugs or antibiotics or probiotics in the past two weeks, and patients who could not give informed consent. Written informed consent was obtained from all patients before enrol...