Download The gut microbiome analysis as source of (un)

Title: The gut microbiome analysis as source of (un)identified resistance genes & (non-)cultivable species
Collaborators: Dr. John Penders, Molecular epidemiologist, Dr. Petra Wolffs, Medical Molecular Microbiologist,
Prof. dr. Paul Savelkoul, Head of dept. medical microbiology, MUMC+ Maastricht,
Proposal (250 words)
Introduction: The gastrointestinal tract is an open system, which every day encounters a myriad of bacterial
acquisitions originating from the environment (e.g. from food, water, soil, and other humans or animals). These
incoming bacteria may harbor pathogenic bacteria; antibiotic resistance genes; virulence genes. In case of
opportunistic pathogens of environmental or food-borne origin, such AMR/virulent bacteria can pose a direct
threat to the host.
Alternatively, these incoming microbes might transfer their resistance/virulence elements through horizontal
gene transfer to the indigenous microbial communities.
It remains largely unknown to which extent exposure to an endemic area, such as during travel to resourcelimited countries or admission to health-care facilities, poses a risk, as the presence of resistant/virulent
bacteria in the human microbiota pose and effect on human/animal health or remain undetected unless they
cause manifest infections.
The human microbiota, in particular within the gastrointestinal tract, warrants special attention as perhaps the
most accessible reservoir of (unkown) resistance genes in the bacterial community due to the high likelihood of
contact and genetic exchange with potential pathogens.
The majority of indigenous microbes cannot be cultivated, and it’s only since the recent application of
sequencing/molecular profiling techniques that the human microbiota has been described in all complexity
including the unculturable and rare taxa. Consequently, it is crucial to study the AMR (resistome) /virulence
potential of the complete indigenous microbiota by applying molecular metagenomic approaches. By knowing
the routes and arsenal of resistance genes in the gastrointestinal tract of humans and animals it can be
anticipated on directly with treatment strategies and recognition of selection of specific genes.
Hypothesis and Objectives:
Antimicrobial resistance (AMR), one of the biggest global public health threats, jeopardizes effective prevention
and treatment of an ever-increasing range of infections.
Adequate surveillance of AMR is a prerequisite for informing global strategies, monitoring the effectiveness of
interventions and detecting new trends and threats. So far, surveillance of AMR has been focused on clinical
relevant pathogens or indicator organisms, thereby neglecting the full resistance potential in microbial
ecosystems such as the gut microbiome of man and animal.
Objectives:
i.
Microbiome analysis in man an animals
ii.
surveillance of acquisition of known and newly identified AMR genes from
with particular focus on the human-animal- environment interface.
high-risk environments
iii.
unraveling the extent to which risk factors contribute to dissemination of
risk environments, and;
AMR from high to low-
iv.
identifying targets to prevent AMR acquisition.
Setting and Methods:
Department of Medical Microbiology MUMC+.
Techniques available:
NGS sequencing pipelines, Reistome PCR analysis, Real time PCR, Bacterial microbiome profiling; multilayer
resistome analysis.
Requirements candidate: Molecular microbiologist; biooinformatician; epidemiologist
Keywords: Microbiome, antibiotic resistance; resistome; NGS; profiling
Selected publications:
von Wintersdorff CJ, Wolffs PF, Savelkoul PHM, Nijsen RR, Lau S, Gerhold K, Hamelmann E, Penders J. The gut
resistome is highly dynamic during the first months of life. Future Microbiol. 2016 Apr;11:501-10. doi:
10.2217/fmb.15.154. Epub 2016 Apr 11.
Janssens PL, Penders J, Hursel R, Budding AE, Savelkoul PHM, Westerterp-Plantenga MS. Long-Term Green
Tea Supplementation Does Not Change the Human Gut Microbiota. PLoS One. 2016 Apr 7;11(4):e0153134.
doi: 10.1371/journal.pone.0153134. eCollection 2016.
von Wintersdorff CJ, Penders J, van Niekerk JM, Mills ND, Majumder S, van Alphen LB, Savelkoul PHM,
Wolffs PF. Dissemination of Antimicrobial Resistance in Microbial Ecosystems through. Horizontal Gene
Transfer. Front Microbiol. 2016 Feb 19;7:173. doi: 10.3389/fmicb.2016.00173. eCollection 2016.
Kluytmans-van den Bergh MF, Huizinga P, Bonten MJ, Bos M, De Bruyne K, Friedrich AW, Rossen JW,
Savelkoul PHM, Kluytmans JA. Presence of mcr-1-positive Enterobacteriaceae in retail chicken meat but not
in humans in the Netherlands since 2009. Euro Surveill. 2016 Mar 3;21(9). doi: 10.2807/15607917.ES.2016.21.9.30149.
van Best N, Hornef MW, Savelkoul PHM, Penders J. On the origin of species: Factors shaping the
establishment of infant’s gut microbiota. Birth Defects Res C Embryo Today. 2015 Dec;105(4):240-51. doi:
10.1002/bdrc.21113. Epub 2015 Nov 26
Mbakwa CA, Penders J, Savelkoul PHM, Thijs C, Dagnelie PC, Mommers M, Arts IC. Gut colonization with
methanobrevibacter smithii is associated with childhood weight development. Obesity (Silver Spring). 2015
Dec;23(12):2508-16. doi: 10.1002/oby.21266. Epub 2015 Nov 2.
Aguirre M, Eck A, Koenen ME, Savelkoul PHM, Budding AE, Venema K. Diet drives quick changes in the
metabolic activity and composition of human gut microbiota in a validated in vitro gut model. Res Microbiol.
2016 Feb-Mar;167(2):114-25. doi: 10.1016/j.resmic.2015.09.006.Epub 2015 Oct 24.
Tedjo DI, Jonkers DM, Savelkoul PHM, Masclee AA, van Best N, Pierik MJ, Penders J. The effect of sampling
and storage on the fecal microbiota composition in healthy and diseased subjects. PLoS One. 2015 May
29;10(5):e0126685. doi: 10.1371/journal.pone.0126685.