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Nat Microbiol. 2018 Nov;3(11):1255-1265. doi: 10.1038/s41564-018-0257-9. Epub 2018 Oct 22.

Recovery of gut microbiota of healthy adults following antibiotic exposure.

Palleja A1,2, Mikkelsen KH3, Forslund SK4,5,6,7,8, Kashani A1,9, Allin KH1,10, Nielsen T1, Hansen TH1, Liang S11,12, Feng Q11,12, Zhang C11,12, Pyl PT1, Coelho LP8, Yang H11,12,13, Wang J11,12,13, Typas A8,14, Nielsen MF3, Nielsen HB2, Bork P5,8,15,16, Wang J17,18,19,20, Vilsbøll T3, Hansen T1,21, Knop FK22,23,24, Arumugam M25, Pedersen O26.

Author information

1
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
2
Clinical-Microbiomics A/S, Copenhagen, Denmark.
3
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
4
Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Berlin, Germany.
5
Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
6
Charité-Universitätsmedizin Berlin , Freie Universität Berlin Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
7
Berlin Institute of Health, Berlin, Germany.
8
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
9
Danish Diabetes Academy, Odense, Denmark.
10
Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
11
BGI-Shenzhen, Shenzhen, China.
12
China National GeneBank, BGI-Shenzhen, Shenzhen, China.
13
James D. Watson Institute of Genome Sciences, Hangzhou, China.
14
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
15
Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany.
16
Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany.
17
iCarbonX, Shenzhen, China.
18
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
19
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
20
State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa Macau, China.
21
Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
22
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. filipknop@dadlnet.dk.
23
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. filipknop@dadlnet.dk.
24
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. filipknop@dadlnet.dk.
25
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. arumugam@sund.ku.dk.
26
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. oluf@sund.ku.dk.

Abstract

To minimize the impact of antibiotics, gut microorganisms harbour and exchange antibiotics resistance genes, collectively called their resistome. Using shotgun sequencing-based metagenomics, we analysed the partial eradication and subsequent regrowth of the gut microbiota in 12 healthy men over a 6-month period following a 4-day intervention with a cocktail of 3 last-resort antibiotics: meropenem, gentamicin and vancomycin. Initial changes included blooms of enterobacteria and other pathobionts, such as Enterococcus faecalis and Fusobacterium nucleatum, and the depletion of Bifidobacterium species and butyrate producers. The gut microbiota of the subjects recovered to near-baseline composition within 1.5 months, although 9 common species, which were present in all subjects before the treatment, remained undetectable in most of the subjects after 180 days. Species that harbour β-lactam resistance genes were positively selected for during and after the intervention. Harbouring glycopeptide or aminoglycoside resistance genes increased the odds of de novo colonization, however, the former also decreased the odds of survival. Compositional changes under antibiotic intervention in vivo matched results from in vitro susceptibility tests. Despite a mild yet long-lasting imprint following antibiotics exposure, the gut microbiota of healthy young adults are resilient to a short-term broad-spectrum antibiotics intervention and their antibiotics resistance gene carriage modulates their recovery processes.

PMID:
30349083
DOI:
10.1038/s41564-018-0257-9

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