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

Tatiana V. Grigoryeva ,Alexander V. Pavlenko ,Evgenii I. Olekhnovich ,Andrey K. Larin ,Maria Markelova ,Р. А. Абдулхаков ,Eugenia A. Boulygina ,Elizaveta V. Starikova ,Maja V. Malakhova ,Alexander V. Tyakht ,Sergey Malanin ,Vadim M. Govorun ,С. Р. Абдулхаков ,Alexander I. Manolov ,Nikita Prianichnikov ,Oksana E. Glushchenko ,Elena N. Ilina ,Boris A. Kovarsky ,Dilyara Safina ,Vlad V. Babenko ,Dilyara Khusnutdinova ,Andrei E. Samoilov ,Elena S. Kostryukova

doi:10.3389/fmicb.2019.01902

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 Helicobacter pylori (HP) eradication therapy. Using approaches for metagenomic data analysis we revealed a statistically significant decrease in alpha-diversity and relative abundance of Bifidobacterium adolescentis due to HP eradication therapy, while the relative abundance of Enterococcus faecium increased. We have detected changes in general metagenome resistome profiles as well: after HP eradication therapy, the ermB, CFX group, and tetQ genes were overrepresented, while tetO and tetW 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 ermB 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 E. faecium strains isolated from stool samples obtained after HP eradication have manifested greater antibiotic resistance in vitro in comparison to other isolates, as well as the higher number of ARGs conferring resistance to macrolides and tetracyclines.

Highlights

Up to 50% of the human population are hosts of Helicobacter pylori (HP), which can provoke a wide range of gastrointestinal diseases, including chronic gastritis, stomach ulcers, duodenal ulcers, gastric cancer, and lymphoma of mucin-associated lymphoid tissue (Covacci et al, 1999; Sanders and Peura, 2002)
We have found six publications describing the investigation of human intestinal microbiota under HP eradication therapy using metagenomic approaches
The microbial community has changed toward the reduction of overall metabolic potential and the increase of potential survival mechanisms. With such a hard antibacterial pressure, the community is restructured, many bacteria can survive, and there is a probability of the emergence of bacteria with multiple antibiotic resistance

Summary

Introduction

Up to 50% of the human population are hosts of Helicobacter pylori (HP), which can provoke a wide range of gastrointestinal diseases, including chronic gastritis, stomach ulcers, duodenal ulcers, gastric cancer, and lymphoma of mucin-associated lymphoid tissue (Covacci et al, 1999; Sanders and Peura, 2002). This bacterium is associated with iron-deficiency anemia, Werlhof disease in Impact of HP Eradication on Gut Microbiota children (Queiroz et al, 2013), nutritional anemia due to vitamin B12 deficiency, thrombocytopenic purpura, and lipid, and glucose metabolism disorders (Buzás, 2014). ARGs can be transferred among bacteria by mobile genetic elements, bacteriophages, and as the result of natural transformation (Davies and Davies, 2010; Schjørring and Krogfelt, 2011; Smillie et al, 2011)

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Conclusion