The antibiotic resistome and microbiota landscape of refugees from Syria, Iraq and Afghanistan in Germany

Robert Häsler¹, Christian Kautz², Ateequr Rehman¹, Rainer Podschun³, Volker Gassling⁴, Pius Brzoska⁵, Jon Sherlock⁵, Jan-Thorsten Gräsner⁶, Gesine Hoppenstedt¹, Sabine Schubert³, Astrid Ferlinz⁷, Wolfgang Lieb⁸, Matthias Laudes⁸, Femke-Anouska Heinsen¹, Jens Scholz⁶, Dag Harmsen⁹, Andre Franke¹, Swantje Eisend¹⁰, Thomas Kunze², Helmut Fickenscher³, Stephan Ott¹⁰, Philip Rosenstiel¹¹, Stefan Schreiber^{12

13}

Affiliations

¹ Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Christian Albrecht University of Kiel, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
² Pharmaceutical Institute, Department of Clinical Pharmacy, Christian Albrecht University of Kiel, Kiel, Germany.
³ Institute of Infection Medicine, Christian Albrecht University of Kiel, Kiel, Germany.
⁴ Department of Oral and Maxillofacial Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany.
⁵ Thermo Fisher Scientific, San Francisco, CA, USA.
⁶ Department of Anaesthesia and Intensive Care Medicine, University Hospital of Schleswig-Holstein, Kiel, Germany.
⁷ Thermo Fisher Scientific, Life Technologies GmbH, Darmstadt, Germany.
⁸ POPGEN Biobank and Institute of Epidemiology, Christian Albrecht University of Kiel, Kiel, Germany.
⁹ Department of Periodontology and Restorative Dentistry, University Hospital Münster, Münster, Germany.
¹⁰ Department of Internal Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
¹¹ Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Christian Albrecht University of Kiel, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. p.rosenstiel@mucosa.de.
¹² Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Christian Albrecht University of Kiel, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. s.schreiber@mucosa.de.
¹³ Department of Internal Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. s.schreiber@mucosa.de.

PMID: 29458422
PMCID: PMC5819293
DOI: 10.1186/s40168-018-0414-7

The antibiotic resistome and microbiota landscape of refugees from Syria, Iraq and Afghanistan in Germany

Robert Häsler et al. Microbiome. 2018.

. 2018 Feb 20;6(1):37.

doi: 10.1186/s40168-018-0414-7.

Authors

Affiliations

¹ Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Christian Albrecht University of Kiel, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
² Pharmaceutical Institute, Department of Clinical Pharmacy, Christian Albrecht University of Kiel, Kiel, Germany.
³ Institute of Infection Medicine, Christian Albrecht University of Kiel, Kiel, Germany.
⁴ Department of Oral and Maxillofacial Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany.
⁵ Thermo Fisher Scientific, San Francisco, CA, USA.
⁶ Department of Anaesthesia and Intensive Care Medicine, University Hospital of Schleswig-Holstein, Kiel, Germany.
⁷ Thermo Fisher Scientific, Life Technologies GmbH, Darmstadt, Germany.
⁸ POPGEN Biobank and Institute of Epidemiology, Christian Albrecht University of Kiel, Kiel, Germany.
⁹ Department of Periodontology and Restorative Dentistry, University Hospital Münster, Münster, Germany.
¹⁰ Department of Internal Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
¹¹ Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Christian Albrecht University of Kiel, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. p.rosenstiel@mucosa.de.
¹² Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Christian Albrecht University of Kiel, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. s.schreiber@mucosa.de.
¹³ Department of Internal Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. s.schreiber@mucosa.de.

PMID: 29458422
PMCID: PMC5819293
DOI: 10.1186/s40168-018-0414-7

Abstract

Background: Multidrug-resistant bacteria represent a substantial global burden for human health, potentially fuelled by migration waves: in 2015, 476,649 refugees applied for asylum in Germany mostly as a result of the Syrian crisis. In Arabic countries, multiresistant bacteria cause significant problems for healthcare systems. Currently, no data exist describing antibiotic resistances in healthy refugees. Here, we assess the microbial landscape and presence of antibiotic resistance genes (ARGs) in refugees and German controls. To achieve this, a systematic study was conducted in 500 consecutive refugees, mainly from Syria, Iraq, and Afghanistan and 100 German controls. Stool samples were subjected to PCR-based quantification of 42 most relevant ARGs, 16S ribosomal RNA gene sequencing-based microbiota analysis, and culture-based validation of multidrug-resistant microorganisms.

Results: The fecal microbiota of refugees is substantially different from that of resident Germans. Three categories of resistance profiles were found: (i) ARGs independent of geographic origin of individuals comprising BIL/LAT/CMA, ErmB, and mefE; (ii) vanB with a high prevalence in Germany; and (iii) ARGs showing substantially increased prevalences in refugees comprising CTX-M group 1, SHV, vanC1, OXA-1, and QnrB. The majority of refugees carried five or more ARGs while the majority of German controls carried three or less ARGs, although the observed ARGs occurred independent of signatures of potential pathogens.

Conclusions: Our results, for the first time, assess antibiotic resistance genes in refugees and demonstrate a substantially increased prevalence for most resistances compared to German controls. The antibiotic resistome in refugees may thus require particular attention in the healthcare system of host countries.

Keywords: Antibiotic resistance; Human; Refugees; Resistome.

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Conflict of interest statement

Ethics approval and consent to participate

All participants gave informed consent, and the study protocol was approved by the local ethical committee at the Medical Faculty of Christian Albrecht University Kiel (D537/15; D501/14). The study does not contain identifiable information of individual persons.

Competing interests

Pius Brzoska, Jon Sherlock, and Astrid Ferlinz are employees of Thermo Fisher, but the company did not influence any aspect of the study. The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Cohort composition. a The number of individuals included in the study from different countries; countries with less than 20 individuals participating are not shown. b Different body sites sampled as part of the study. c Age distribution of the individuals included in the study, color coded by country. For better visualization, values were binned with 2 years per bin

**Fig. 2**
Antibiotic resistances in stool samples from refugees and German control individuals. a Prevalences; bar heights represent prevalences relative to German control individuals, color coded by resistance gene. Genes were grouped in three categories: bottom group (BIL/LAT/CMY, ErmB, and mefE), present in similar amounts in refugees and German control individuals; middle group (vanB), present in higher amount in German controls; and upper group (QnrB, OXA-1, vanC1, SHV, CTX-M group 1, TEM), present in higher amounts in refugees, while two resistance genes (QnrB and OXA-1) were not found in German control individuals and scaled separately for visualization purposes. b The number of antibiotic resistance genes observed per individual, illustrated by the proportion of individuals per nation with a given number of different resistances. Others: refugees from Albania, Armenia, Chechnya, India, Kosovo, Lebanon, Somalia, Turkey, and Yemen

**Fig. 3**
Signatures of potential pathogens in stool samples from refugees and German control individuals. a Prevalence of 16S rRNA gene fragments indicative of potential pathogens in refugees and German control individuals. Bar heights represent prevalences relative to German control individuals, color coded by potential pathogen. Potential pathogens, which were not found in German control individuals (*Klebsiella pneumoniae*, *Haemophilus influenzae*, *Shigella sonnei*), were scaled separately for visualization purposes. b The number of signatures of potential pathogens observed per individual illustrated by the proportion of individuals per nation with a given number of different potential pathogens. Others: refugees from Albania, Armenia, Chechnya, India, Kosovo, Lebanon, Somalia, Turkey, and Yemen

**Fig. 4**
Stool microbiota composition differences between refugees and German control individuals. a Relative abundances of major bacterial phyla in German control individuals and refugees. Fecal bacterial profiles were generated by 16S rRNA gene amplicon sequencing. b Heatmap of top 10 selected indicator phylotypes, which are more abundant in German control individuals (upper half) and in refugees (lower half), color coded by abundance, which was z-score normalized for better visualization

**Fig. 5**
Regional microbiota differences based on stool 16S rRNA gene analysis. Principal coordinate analysis (PCoA) based on the Bray-Curtis index (a) and on the Jaccard index (b), color coded by origin. Individuals below 10 years of age are labeled specifically. c Variance explained by the individual coordinates, color coded by index measure. Others: refugees from Albania, Armenia, Chechnya, India, Kosovo, Lebanon, Somalia, Turkey, and Yemen

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