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Long-term ecological impacts of antibiotic administration on the human intestinal microbiota
Karolinska Institutet.
Karolinska Institutet.
Karolinska Institutet / Medical Products Agency.
Swedish University of Agricultural Sciences.
2007 (English)In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 1, no 1, 56-66 p.Article in journal (Refereed) Published
Abstract [en]

Antibiotic administration is known to cause short-term disturbances in the microbiota of the human gastrointestinal tract, but the potential long-term consequences have not been well studied. The aims of this study were to analyse the long-term impact of a 7-day clindamycin treatment on the faecal microbiota and to simultaneously monitor the ecological stability of the microbiota in a control group as a baseline for reference. Faecal samples from four clindamycin-exposed and four control subjects were collected at nine different time points over 2 years. Using a polyphasic approach, we observed highly significant disturbances in the bacterial community that persisted throughout the sampling period. In particular, a sharp decline in the clonal diversity of Bacteroides isolates, as assessed by repetitive sequence-based PCR (rep-PCR) and long-term persistence of highly resistant clones were found as a direct response to the antibiotic exposure. The Bacteroides community never returned to its original composition during the study period as assessed using the molecular fingerprinting technique, terminal restriction fragment length polymorphism (T-RFLP). Furthermore, using real-time PCR we found a dramatic and persistent increase in levels of specific resistance genes in DNA extracted from the faeces after clindamycin administration. The temporal variations in the microbiota of the control group were minor compared to the large and persistent shift seen in the exposed group. These results demonstrate that long after the selection pressure from a short antibiotic exposure has been removed, there are still persistent long term impacts on the human intestinal microbiota that remain for up to 2 years post-treatment.

Place, publisher, year, edition, pages
2007. Vol. 1, no 1, 56-66 p.
Keyword [en]
Bacteroides, clindamycin, rep-PCR, faeces, T-RFLP
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:sh:diva-31968DOI: 10.1038/ismej.2007.3ISI: 000249215800009PubMedID: 18043614ScopusID: 2-s2.0-34248152283OAI: oai:DiVA.org:sh-31968DiVA: diva2:1072079
Note

Som manuskript i avhandling. As manuscript in dissertation.

Erratum: Jernberg, C., Löfmark, S., Edlund, C., & Jansson, J. K. (2013). Erratum: Long-term ecological impacts of antibiotic administration on the human intestinal microbiota (ISME journal (2007) 1 (56-66) DOI: 10.1038/ismej.2007.3). ISME Journal, 7(2), 456. doi:10.1038/ismej.2012.91

Available from: 2017-02-07 Created: 2017-02-06 Last updated: 2017-02-08Bibliographically approved
In thesis
1. Use of microbiomics to study human impacts on complex microbial communities
Open this publication in new window or tab >>Use of microbiomics to study human impacts on complex microbial communities
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The study of bacterial communities in nature is currently a challenge. The majority of bacteria in clinical and environmental samples have not yet been cultured and therefore we cannot fully understand their roles in nature and how the ecological balance in a specific microbial ecosystem can be disrupted. For example, exposure to pollutants in soil and antibiotics in the human gut can have large consequences on microbial populations but the magnitude of these impacts is difficult to assess. In this thesis, a combination of molecular techniques, microbiomics, were used to assess complex microbial communities in soil and the human gut. One goal of this thesis was to study the impact of the toxic compound, 4-chlorophenol, on the soil microbiota. In addition, a specific 4-chlorophenol degrading bacterium, Arthrobacter chlorophenolicus, was monitored in soil. In order to monitor the cells they were chromosomally tagged with marker genes encoding either the green fluorescent protein (the gfp gene) or firefly luciferase (the luc gene). During degradation of high levels of 4-chlorophenol in soil, total cells counts of A. chlorophenolicus cells could be measured by flow cytometry (GFP protein) and the metabolic activity could be measured by lurninometry (luciferase activity). In addition, the relative abundance of A. chlorophenolicus in soil could be measured by terminal restriction fragment length polymorphism (T-RFLP) and a higher relative abundance was detected in soil contaminated with 4chlorophenol compared with non-treated soil. The impacts of 4-chlorophenol and A. chlorophenolicus on the dominant members of the soil microbiota were also assessed by T-RFLP. Another goal of this thesis was to study the impact of a short term antibiotic administration in a long term perspective, using either clindamycin, in a two year study or a triple therapy for eradication of Helicobacter pylori containing clarithromycin and metronidazole, in a four year study, on the human fecal microbiota. Both the total bacterial community and specific populations, i.e. Bacteroides spp. and Enterococcus spp., were monitored by T-RFLP. The Bacteroides populations never returned to their pre-treatment composition after clindamycin exposure during the two year study period. Selection and persistence of resistant Bacteroides clones up to two years after treatment was furthermore detected. In the four year study, Enterococcus populations increased as a response to the clarithromycin and metronidazole treatment. An increase in the levels of antibiotic resistance genes, specific erm genes, conferring resistance to macrolides and lincosamides were detected for up to 2 and 4 years after both types of antibiotic treatments in the respective studies. It was also possible to specifically monitor two probiotic Lactobacillus strains and their transient colonization by T-RFLP. In conclusion, the use of a polyphasic approach with complementary analytical tools made it possible to obtain a comprehensive picture of complex microbial communities. In addition, specific bacteria of interest in complex soil and fecal samples could be monitored using microbiomics approaches.

Place, publisher, year, edition, pages
Stockholm: Karolinska instiutet, 2006. 37 p.
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-31990 (URN)91-7140-960-2 (ISBN)
Public defence
2006-12-15, MB416, Alfred Nobels allé 7, Huddinge, 10:00 (English)
Opponent
Supervisors
Available from: 2017-02-08 Created: 2017-02-08 Last updated: 2017-02-08Bibliographically approved

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