Comparison of the impact of Helicobacter pylori eradication treatment with bismuth and non-bismuth quadruple regimens on the gut microbiota

Abstract

Background: Helicobacter pylori eradication requires a combination of antibiotics. The short and long-term effect of different H. pylori eradication regimens on the gut microbiota has received little attention. Aims: To evaluate and compare the impact of the two most frequently recommended first-line H. pylori eradication regimens — bismuth and non-bismuth quadruple regimens — on the gut microbiota. Patients and Methods: Two 14-day quadruple treatments were evaluated and compared: bismuth-based quadruple therapy (proton pump inhibitor, bismuth, tetracycline, and metronidazole) and non-bismuth quadruple “concomitant” therapy (proton pump inhibitor, amoxicillin, clarithromycin and metronidazole). Stool samples were collected before, and at two and six months after finishing treatment. Gut microbiota was analyzed from the stool samples by sequencing of the 16S rRNA gene and sample-specific barcode sequences. Results: 51 patients were initially included and 38 completed the six months follow-up. A total of 136 stool samples were analyzed. Eradication rates were similar between treatments (bismuth 90%, non-bismuth 89%). Tolerance was also similar. Both treatment regimens induced a significant decrease in alpha diversity two months after treatment, which was partially recovered at six months. Beta diversity was also similarly affected by both treatments and partially recovered at six months follow-up. Longitudinal pairwise Aichison distances were calculated: large individual variation was observed during treatment and at follow-up for both regimens but the average distance was similar, i.e., 1.70 and 1.74, respectively, at two months after treatment, and 1.19 and 1.14 at six months. Statistically significant changes of specific taxa were also observed and these were different for each treatment. Conclusions: H. pylori eradication using quadruple therapies significantly reduces microbiota diversity, although it is partially recovered six months after the end of treatment. No difference was found between bismuth and non-bismuth quadruple therapies; therefore, other aspects should guide prescription.

Keywords

• microbiota
• antibiotics
• clarithromycin
• bismuth
• proton pump inhibitors
• helicobacter pylori.