Recovery of gut microbiota of healthy adults following antibiotic exposure

Albert Palleja; Kristian H Mikkelsen; Sofia K Forslund; Alireza Kashani; Kristine H Allin; Trine Nielsen; Tue H Hansen; Suisha Liang; Qiang Feng; Chenchen Zhang; Paul Theodor Pyl; Luis Pedro Coelho; Huanming Yang; Jian Wang; Athanasios Typas; Morten F. Nielsen; Henrik Bjorn Nielsen; Peer Bork; Jun Wang; Tina Vilsbøll; Torben Hansen; Filip K Knop; Manimozhiyan Arumugam; Oluf Pedersen

doi:10.1038/s41564-018-0257-9

Recovery of gut microbiota of healthy adults following antibiotic exposure

Albert Palleja, Kristian H Mikkelsen, Sofia K Forslund, Alireza Kashani, Kristine H Allin, Trine Nielsen, Tue H Hansen, Suisha Liang, Qiang Feng, Chenchen Zhang, Paul Theodor Pyl, Luis Pedro Coelho, Huanming Yang, Jian Wang, Athanasios Typas, Morten F. Nielsen, Henrik Bjorn Nielsen, Peer Bork, Jun Wang, Tina VilsbøllTorben Hansen, Filip K Knop, Manimozhiyan Arumugam, Oluf Pedersen

143 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Microbiology
Vol/bind	3
Udgave nummer	11
Sider (fra-til)	1255-1265
Antal sider	11
ISSN	2058-5276
DOI	https://doi.org/10.1038/s41564-018-0257-9
Status	Udgivet - 1 nov. 2018

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10.1038/s41564-018-0257-9

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Palleja, A., Mikkelsen, K. H., Forslund, S. K., Kashani, A., Allin, K. H., Nielsen, T., Hansen, T. H., Liang, S., Feng, Q., Zhang, C., Pyl, P. T., Coelho, L. P., Yang, H., Wang, J., Typas, A., Nielsen, M. F., Nielsen, H. B., Bork, P., Wang, J., ... Pedersen, O. (2018). Recovery of gut microbiota of healthy adults following antibiotic exposure. Nature Microbiology, 3(11), 1255-1265. https://doi.org/10.1038/s41564-018-0257-9

Palleja, A, Mikkelsen, KH, Forslund, SK, Kashani, A, Allin, KH , Nielsen, T, Hansen, TH, Liang, S, Feng, Q, Zhang, C, Pyl, PT, Coelho, LP, Yang, H, Wang, J, Typas, A, Nielsen, MF, Nielsen, HB, Bork, P, Wang, J, Vilsbøll, T , Hansen, T , Knop, FK , Arumugam, M & Pedersen, O 2018, 'Recovery of gut microbiota of healthy adults following antibiotic exposure', Nature Microbiology, bind 3, nr. 11, s. 1255-1265. https://doi.org/10.1038/s41564-018-0257-9

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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.",

author = "Albert Palleja and Mikkelsen, {Kristian H} and Forslund, {Sofia K} and Alireza Kashani and Allin, {Kristine H} and Trine Nielsen and Hansen, {Tue H} and Suisha Liang and Qiang Feng and Chenchen Zhang and Pyl, {Paul Theodor} and Coelho, {Luis Pedro} and Huanming Yang and Jian Wang and Athanasios Typas and Nielsen, {Morten F.} and Nielsen, {Henrik Bjorn} and Peer Bork and Jun Wang and Tina Vilsb{\o}ll and Torben Hansen and Knop, {Filip K} and Manimozhiyan Arumugam and Oluf Pedersen",

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AU - Nielsen, Trine

AU - Hansen, Tue H

AU - Liang, Suisha

AU - Feng, Qiang

AU - Zhang, Chenchen

AU - Pyl, Paul Theodor

AU - Coelho, Luis Pedro

AU - Yang, Huanming

AU - Wang, Jian

AU - Typas, Athanasios

AU - Nielsen, Morten F.

AU - Nielsen, Henrik Bjorn

AU - Bork, Peer

AU - Wang, Jun

AU - Vilsbøll, Tina

AU - Hansen, Torben

AU - Knop, Filip K

AU - Arumugam, Manimozhiyan

AU - Pedersen, Oluf

PY - 2018/11/1

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N2 - 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.

AB - 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.

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DO - 10.1038/s41564-018-0257-9

M3 - Journal article

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SN - 2058-5276

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SP - 1255

EP - 1265

JO - Nature Microbiology

JF - Nature Microbiology

IS - 11

ER -

Recovery of gut microbiota of healthy adults following antibiotic exposure

Abstract

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