Shifts in the Human Gut Microbiota Structure Caused by Quadruple Helicobacter pylori Eradication Therapy

Abstract

The human gut microbiome plays an important role both in health and disease. Use of antibiotics can alter gut microbiota composition, which can lead to various deleterious events. Here we report a whole genome sequencing metagenomic/genomic study of the intestinal microbiota changes caused by <i>Helicobacter pylori</i> (HP) eradication therapy. Using approaches for metagenomic data analysis we revealed a statistically significant decrease in alpha-diversity and relative abundance of <i>Bifidobacterium adolescentis</i> due to HP eradication therapy, while the relative abundance of <i>Enterococcus faecium</i> increased. We have detected changes in general metagenome resistome profiles as well: after HP eradication therapy, the <i>ermB, CFX</i> group, and <i>tetQ</i> genes were overrepresented, while <i>tetO</i> and <i>tetW</i> genes were underrepresented. We have confirmed these results with genome-resolved metagenomic approaches. MAG (metagenome-assembled genomes) abundance profiles have changed dramatically after HP eradication therapy. Focusing on <i>ermB</i> gene conferring resistance to macrolides, which were included in the HP eradication therapy scheme, we have shown a connection between antibiotic resistance genes (ARGs) and some overrepresented MAGs. Moreover, some <i>E. faecium</i> strains isolated from stool samples obtained after HP eradication have manifested greater antibiotic resistance <i>in vitro</i> in comparison to other isolates, as well as the higher number of ARGs conferring resistance to macrolides and tetracyclines.