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Shifts in the gut microbiota structure caused by Helicobacter pylori eradication therapy

Evgenii I. Olekhnovich, Alexander I. Manolov, Nikita A. Prianichniikov, Andrei E. Samoilov, Maja V. Malakhova, Alexander V. Pavlenko, Vlad V. Babenko, Andrei K. Larin, Yuriy Y. Babin, Elizaveta V. Starikova, Dmitry I. Chuvelev, Boris A. Kovarsky, Maria A. Tregubova, Dilyara D. Safina, Maria I. Markelova, Tatiana V. Grigoryeva, Eugenia A. Boulygina, Sergey Yu. Malanin, Rustam A. Abdulkhakov, Sayar R. Abdulkhakov, Elena S. Kostryukova, Elena N. Ilina, Vadim M. Govorun
doi: https://doi.org/10.1101/296426
Evgenii I. Olekhnovich
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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  • For correspondence: olekhnovich@rcpcm.org
Alexander I. Manolov
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Nikita A. Prianichniikov
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Andrei E. Samoilov
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Maja V. Malakhova
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Alexander V. Pavlenko
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Vlad V. Babenko
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Andrei K. Larin
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Yuriy Y. Babin
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Elizaveta V. Starikova
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Dmitry I. Chuvelev
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Boris A. Kovarsky
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Maria A. Tregubova
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Dilyara D. Safina
2Kazan Federal University, 18 Kremlyovskaya, Kazan, 420008, Russia
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Maria I. Markelova
2Kazan Federal University, 18 Kremlyovskaya, Kazan, 420008, Russia
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Tatiana V. Grigoryeva
2Kazan Federal University, 18 Kremlyovskaya, Kazan, 420008, Russia
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Eugenia A. Boulygina
2Kazan Federal University, 18 Kremlyovskaya, Kazan, 420008, Russia
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Sergey Yu. Malanin
2Kazan Federal University, 18 Kremlyovskaya, Kazan, 420008, Russia
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Rustam A. Abdulkhakov
2Kazan Federal University, 18 Kremlyovskaya, Kazan, 420008, Russia
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Sayar R. Abdulkhakov
2Kazan Federal University, 18 Kremlyovskaya, Kazan, 420008, Russia
3Kazan State Medical University, 49 Butlerova, Kazan, 420012, Russia
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Elena S. Kostryukova
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Elena N. Ilina
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Vadim M. Govorun
1Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya 1a, Moscow 119435, Russia
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Abstract

The human gut microbiome plays an important role both in health and disease. The use of antibiotics can alter gut microbiota composition, which can cause complications of various kinds. Here we report a whole genome sequencing metagenomic study of the intestinal microbiota changes caused by Helicobacter pylori eradication therapy. We have found the decrease in taxonomic alpha-diversity due to the therapy. The changes observed were more extensive for patients with duodenal ulcer and female ones. As well across the patients under the therapy we have detected the shifts in the metabolic potential and resistome. Seven KEGG pathways associated with quorum sensing, genetic Information processing and environmental Information processing were increased, while metabolic pathways related with metabolism of cofactors and vitamins and glycan biosynthesis and metabolism decreased. Changes in the resistome profile have also been identified. We observed perturbations in intraspecies structures, which were higher in group of patients under the therapy than in control group of people without treatment. The Eubacterium rectale pangenome extracted from metagenomic data were changed. We also isolated and sequenced Enterococcus faecium strains from two patients before and after eradication therapy. After the therapy this bacterium increased as the antibiotic resistance in vitro, as well the number of ARGs to macrolides and tetracyclines and metagenomic relative abundance in comparison with strains before therapy. In summary, microbial community demonstrated shift to reduce metabolic potential and to increased mechanisms, which mediate more survival condition through intraspecies perturbations.

Importance The human gut microbiome plays an important role both in health and disease. The use of antibiotics can alter gut microbiota composition, which can cause complications of various kinds. H. pylori eradication therapy causes multiple shifts and alterations (including intraspecies changes) of the intestinal microbiota structure and leads to the accumulation of genes which determine resistance to macrolides. Since these changes are not the same for patients with various diseases, patients with duodenal ulcer may be further paid special attention for reducing side effects, such as antibiotic-induced dysbiosis. Also, study of antibiotic treatment in terms of its impact upon the human gut microbiota allows shedding light on of the complex processes that cause accumulation and spread of antibiotic resistance. An identification and understanding of these complicated processes may help to constrain antibiotic resistance spread, which is of great importance for human health care.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 26, 2018.
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Shifts in the gut microbiota structure caused by Helicobacter pylori eradication therapy
Evgenii I. Olekhnovich, Alexander I. Manolov, Nikita A. Prianichniikov, Andrei E. Samoilov, Maja V. Malakhova, Alexander V. Pavlenko, Vlad V. Babenko, Andrei K. Larin, Yuriy Y. Babin, Elizaveta V. Starikova, Dmitry I. Chuvelev, Boris A. Kovarsky, Maria A. Tregubova, Dilyara D. Safina, Maria I. Markelova, Tatiana V. Grigoryeva, Eugenia A. Boulygina, Sergey Yu. Malanin, Rustam A. Abdulkhakov, Sayar R. Abdulkhakov, Elena S. Kostryukova, Elena N. Ilina, Vadim M. Govorun
bioRxiv 296426; doi: https://doi.org/10.1101/296426
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Shifts in the gut microbiota structure caused by Helicobacter pylori eradication therapy
Evgenii I. Olekhnovich, Alexander I. Manolov, Nikita A. Prianichniikov, Andrei E. Samoilov, Maja V. Malakhova, Alexander V. Pavlenko, Vlad V. Babenko, Andrei K. Larin, Yuriy Y. Babin, Elizaveta V. Starikova, Dmitry I. Chuvelev, Boris A. Kovarsky, Maria A. Tregubova, Dilyara D. Safina, Maria I. Markelova, Tatiana V. Grigoryeva, Eugenia A. Boulygina, Sergey Yu. Malanin, Rustam A. Abdulkhakov, Sayar R. Abdulkhakov, Elena S. Kostryukova, Elena N. Ilina, Vadim M. Govorun
bioRxiv 296426; doi: https://doi.org/10.1101/296426

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