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Early-Life Antibiotic Use Affects Gut Microbiome Composition, New Study Says

NEW YORK (GenomeWeb) – Antibiotic use early in life leaves its mark on the gut microbiome, according to a team of Finnish researchers.

Children who've taken macrolide antibiotics like azithromycin and clarithromycin experience long-lived shifts in their gut microbiome makeups, the University of Helsinki's Willem de Vos and his colleagues reported today in Nature Communications. They combined phylogenetic and metagenomic analysis of the intestinal microbiomes of some 236 Finnish children with antibiotic purchase records to find that the microbiomes of kids who've taken macrolides contain fewer Actinobacteria, but more Bacteroidetes and Proteobacteria. Macrolide use was further linked with an increased risk of asthma and weight gain.

"[M]acrolide use may have undesired effects on the developing microbiota of children, which may compromise the development of a healthy immune system and metabolism," de Vos and his colleagues wrote in their paper.

The researchers analyzed the intestinal microbiomes of 236 Finnish children between the ages of two and seven who all attended the same daycare facility. The team collected 257 fecal samples from the children, with some kids providing two samples some seven months apart.

These samples were then grouped based on the child's antibiotic use, as determined from health records. Most antibiotics were prescribed for respiratory infections. Control samples were from children who hadn't used antibiotics for more than two years and who'd had less than one course of antibiotics each year, on average. Nearly all the children had been breast-fed for at least six months.

Based on 454 sequencing of the 16S rRNA gene, the researchers determine the samples' bacterial compositions. The children who had had macrolide antibiotics within the previous sixth months had a distinctive microbiome, de Vos and his colleagues reported. In particular, they had reduced levels of Actinobacteria, including Bifidobacterium, and increased levels of Bacteroidetes and Proteobacteria.

These differences, the researchers noted, were largely resolved in the microbiomes of children who'd taken macrolides in the past year or two years. Additionally, children who'd taken penicillin didn't exhibit such distinctive changes.

Though the microbiome composition of children who'd taken macrolides tended to bounce back, the researchers reported that macrolide use was still associated with a long-term decrease in microbial richness. Even the microbiomes of children who'd taken macrolides one year to two years previously didn't reach the richness levels of control microbiomes.

In particular, they found that Bifidobacterium and Bacteroides levels normalized within a year, but that the abundance of Collinsella, Lactobacillus, and Anaerostipes remained low after two years.

Macrolide resistance was also increased in the microbiomes of children who'd taken those antibiotics. A combination of culture- and qPCR-based analysis found that macrolide resistance and the expression of resistance genes increased after taking such antibiotics then declined to a low level some six to 12 months later.

Additionally, bile salt hydrolases weredecreased in children who'd taken macrolides. Bile salt metabolism, the researchers noted, is an important function of the gut microbiome and affects host energy and metabolism.

A full recovery from macrolide use, the researchers added, appears to take longer than the average interval between courses.

Frequent macrolide use during the first two years of life was also linked with developing asthma and becoming overweight, de Vos and his colleagues found. Children who'd taken macrolides more than two times before their second birthday were much more likely, given an odds ratio of 6.11, to develop asthma as kids who hadn't taken macrolides.

They also found that the microbiomes of children with asthma differed from those of healthy controls as they contained different abundance levels of Blautia, Rothia, and Coprobacillus.

Similarly, the microbiomes of overweight children had differing levels of Clostridium (Erysipelotrichaceae), Clostridium (Clostridiaceae), Akkermansia, and Enterococcus than matched healthy controls.

"Our results show that macrolide use in childhood is associated with long-term distortions in the composition, function, and antibiotic resistance of the intestinal microbiota," de Vos and his colleagues wrote.