The use of the antibiotic macrolide in two to seven years old Finnish children is associated with a long-lasting shift in their intestinal bacterial composition. Researchers from Finland (Helsinki and Turku), Germany (Heidelberg) and the Netherlands (Wageningen) found that the microbiota shift decreases the abundance of potential beneficial bacteria and stimulates that of the undesired microorganisms associated with weight gain and increased risk of asthma in later life.

The scientific findings are published in Nature Communicationsby Katri Korpela and a team led by Willem M. de Vos (Wageningen University and University of Helsinki) with colleagues in Finland, the Netherlands and Germany (EMBL Heidelberg). The publication brings insight in the impact of antibiotics on human. The team studied a well-controlled cohort of pre-school children (142 children, 2-7 years old) who for instance received the same day-care meals, and recorded their antibiotic use (especially against the high prevailing ototis – inflammation of the ear), and health status. The research team coupled these to deep and global analysis of the intestinal microbiota and its functions.

The team confirms the strong association between antibiotic use in early life and later life health. They refined this relation by showing the largest effects of macrolide antibiotics, such as azithromycin and clarithromycin rather than penicillins, such as ampicillin, or other antibiotics on an increase in body mass index (BMI) as well as asthma incidence.

Remarkably, a similar strong effect of macrolide but not the other antibiotics, was detected on the intestinal microbiota. In addition, a likely causal relation between the use of the antibiotics and antibiotic resistance was established. This means that a selection of ‘bad’ bacteria gradually takes place in the intestine.

Moreover, the researchers were able to identify a series of bacteria that could explain best the increased BMI. These included several bacterial groups that had been implicated in obesity development, such as a decreased level of Akkermansia, a species earlier discovered in Wageningen and curbing obesity development in mice.

Finally, the researchers found that the use of macrolides was associated with a decreased level of bile salt hydrolase, en enzyme in the intestinal microbiome, indicative of signaling between the host produced bile via the enzymatic activity of the intestinal microbiota and important regulators. Earlier animal experiments of the APC group in Cork Ireland have shown that increasing the level of bile salt hydrolase decreased diet-induced obesity in mice.

Te research results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.

Publication
Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Katri Korpela, Anne Salonen, Lauri J. Virta, Riina A. Kekkonen, Kristoffer Forslund, Peer Bork & Willem M. de Vos. Nature Communications 26 January 2016.