Eradication of Helicobacter pylori reshapes gut microbiota and facilitates the evolution of antimicrobial resistance through gene transfer and genomic mutations in the gut.

Abstract

Treating Helicobacter pylori (H. pylori) infection requires large quantities of antibiotics, thus dramatically promoting the enrichment and dissemination of antimicrobial resistance (AMR) in feces. However, the influence of H. pylori eradication on the AMR mobility and the gut microbiota evolution has yet to be thoroughly investigated. Here, a study involving 12 H. pylori-positive participants was conducted, and the pre- and post- eradication fecal samples were sequenced. Metagenomic analysis revealed that the eradication treatment drastically altered the gut microbiome, with the Escherichia and Klebsiella genera emerging as the predominant bacteria. Interestingly, the eradication treatment significantly increased the relative abundance and diversity of resistome and mobilome in gut microbiota. Eradication of H. pylori also enriched AMR genes (ARGs) conferring resistance to antibiotics not administered because of the co-location with other ARGs or mobile genetic elements (MGEs). Additionally, the Escherichia and Klebsiella genera were identified as the primary bacterial hosts of these highly transferable ARGs. Furthermore, the genomic variations associated with ARGs in Escherichia coli (E. coli) caused by the eradication treatment were profiled, including the parC, parE, and gyrA genes. These findings revealed that H. pylori eradication promoted the enrichment of ARGs and MGEs in the Escherichia and Klebsiella genera, and further facilitated bacterial evolution through the horizontal transfer of ARGs and genomic variations.