Metagenomic Changes of Gut Microbiota following Treatment of Helicobacter pylori Infection with a Simplified Low-Dose Quadruple Therapy with Bismuth or Lactobacillus reuteri

Abstract

Background: Probiotic supplementation to antibiotic regimens against Helicobacter pylori infection has been proposed to improve eradication rate and to decrease detrimental effects on gut microbiota. Aims: To evaluate microbiota modifications due to a low-dose quadruple therapy with bismuth or Lactobacillus reuteri. Methods: Forty-six patients infected with H. pylori were prospectively enrolled in a single-centre, randomized controlled trial to receive b.i.d. with meals for 10 days low-dose quadruple therapy consisting of rabeprazole 20 mg and bismuth (two capsules of Pylera® plus 250 mg each of tetracycline and metronidazole), or the same dose of rabeprazole and antibiotics plus Gastrus® (L. reuteri), one tablet twice-a-day for 27 days. Stool samples were collected at the enrolment, at the end and 30–40 days after the treatment. Gut microbiota composition was investigated with 16S rRNA gene sequencing. Results: Eradication rate was by ITT 78% in both groups, and by PP analysis 85.7% and 95.5% for Gastrus® and bismuth group, respectively. Alpha and beta diversity decreased at the end of treatment and was associated with a reduction of bacterial genera beneficial for gut homeostasis, which was rescued 30–40 days later in both groups, suggesting a similar impact of the two regimens in challenging bacterial community complexity. Conclusions: Low-dose bismuth quadruple therapy proved to be effective with lower costs and amount of antibiotics and bismuth. Gastrus® might be an option for patients with contraindications to bismuth. L. reuteri was unable to significantly counteract dysbiosis induced by antibiotics. How to administer probiotics to prevent gut microbiota alterations remains an open question.

Metaproteomic assessment of gut microbial and host functional perturbations in Helicobacter pylori -infected patients subjected to an antimicrobial protocol

“…These data confirm and extend the dynamics observed in a slightly larger cohort of patients (including those analyzed in this work) in our recent study based on 16S rRNA gene amplicon sequencing. 9 Specifically, in both studies we consistently found an increase in Proteobacteria, Lactobacillales, and Enterococcus following therapy. However, compared to the metaproteomics data, 16S rRNA gene sequencing enabled us to detect a larger number of genera reduced at T1 compared to T0.…”

“…Nineteen adult patients diagnosed with H. pylori infection were recruited at the Department of Internal Medicine, Gastroenterology section, University of Sassari, Italy, in the context of a larger study described elsewhere. 9 Patients were defined as positive for H. pylori infection based on its detection in gastric specimens and/or a positive 13 C-Urea Breath Test 13 C-UBT) and/or a positive stool antigen test. The exclusion criteria were as follows: pregnancy or lactation, clinically significant diseases, recent gastroenteritis or bowel preparation for colonoscopy, history of drug or alcohol abuse, and use of antibiotics or probiotics within the month preceding the enrollment.…”

“…The treatment included the antibiotics tetracycline and metronidazole, supplemented with bismuth subcitrate potassium and rabeprazole, and was effective in all patients under study. 9 Here, we describe the changes occurring to GM structure and functions in a subgroup of the same patient cohort after H. pylori eradication therapy. The application of metaproteomics to patients’ stool samples also enabled us to monitor host fecal proteome variations and their correlation with microbial community modifications.…”

Benchmarking low- and high-throughput protein cleanup and digestion methods for human fecal metaproteomics

“…The fecal samples used in this study were obtained as part of a larger collaborative study ( 27 ) that was approved by the Institutional Review Board of the local Ethics Committee (ASL n. 1 Sassari, Prot. No.…”