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At bacterial and national population level, the length of availability of
veterinary antibiotics is linked to the resistance potential of the human gut
flora
A group of molecular biologists and microbiologists from several European countries
has just published the results of a study assessing the country-specific effect of antibiotic
use on the gut flora of individuals.
The analyses were based on new high-throughput sequencing techniques, allowing to extract
and sequence all the DNA present in a sample, and to identify the species present (DNA of
the host, in this case humans, but also of any bacterial or viral species). They conducted these
tests on stool samples of volunteers from different countries: Denmark (n=71), Spain (n=39)
and the USA (n=142).
They obtained a set of DNA of bacterial species in the intestines (microbiota) for each
volunteer. In parallel, they used a known catalogue of genes for resistance to antibiotics: they
identified 380 ‘resistance determinants’ (genetic sequences coding for a resistance
mechanism), linked to 68 classes and subclasses of antibiotics (resistance to a class uses a
common mechanism).
In this manner, they identified an average of 21 resistance determinants per microbiota.
Among the classes of antibiotics for which there is at least one resistance gene in each
microbiota, they selected those that are authorised in veterinary medicines or those that have
an authorised veterinary equivalent. The authors show that, in this study, the frequency of
resistance genes in human microbiota to classes of authorised veterinary antibiotics is
significantly higher than to molecules restricted to human use (see graph).
This result may be biased, as volunteers are not necessarily representative of a country. This
does not preclude the finding that ‘the use of antibiotics in animals contributes to the
development of resistance in human commensal bacteria’, which the authors consider to be a
‘robust trend.’
The authors then looked at the different resistance profiles of the digestive flora in the country
of origin of the volunteers. They noted that the ‘Spanish flora’ present a higher frequency of
resistance than those of American or Danish origin. Specificities were highlighted according
to geography: e.g. American flora has a rather marked tendency of resistance to macrolides,
lincosamides and streptogramines, as well as cephalosporins. For the Danish samples, the
flora has a higher proportion of resistance genes to bacitracin, vancomycin ‘and to a lesser
extent, to streptomycin, spectinomycin and chloramphenicol.’ The authors indicate that the
presence of genes for resistance to vancomycin in humans could be linked to the use of
avoparcin in animal health (before it was banned) – even though the genes involved are
clearly different. They also fail to mention the ban on chloramphenicol in the EU.
They then added to their study sequencing data from microbiota from other European
countries. They note that subjects from Italy and France have resistance profiles that are
comparable to those from Spain. The authors suggest a difference in nutrition (higher
consumption of unpasteurised or raw food) to explain at least partly this difference between
the North and South of Europe.
The difference in resistance of the flora at a national level are not only correlated with the
consumption of antibiotics in ambulatory care (outside the hospital) but also with the level of
consumption in animal production in the country concerned (ESVAC data). They believe that
these results provide ‘a profound molecular basis for the ongoing debate on the appropriate
use of antibiotics in agriculture and medicine.’
Source:
Country-specific antibiotic use practices impact the human gut resistome. Forslund K et al.
Genome Research. 2013, vol. 23, n° 7, p. 1163-1169.
Figure: Presence of resistance genes according to the use of the corresponding antibiotics in
human and/or animal health