Abstract
Macrolides are among the most widely prescribed antibiotics worldwide. However, their impact on the gut’s bacterial microbiota remains uncertain. We characterised the intestinal microbiota in 6–11 month-old infants in India who received a 3-day course of azithromycin or placebo during a randomised trial of oral poliovirus vaccine immunogenicity (CTRI/2014/05/004588). In 60 infants per study arm, we sequenced the V4 region of the bacterial 16S rRNA gene in stool samples collected before and 12 days after finishing treatment. We also tested for the presence of common bacterial, viral, and eukaryotic enteropathogens in the same samples using real-time PCR in a Taqman array card (TAC) format. Azithromycin induced a modest decline in microbiota richness and a shift in taxonomic composition driven by a reduction in the relative abundance of Proteobacteria and Verrucomicrobia (specifically Akkermansia muciniphila). The former phylum includes pathogenic strains of Escherichia coli and Campylobacter spp. that declined in prevalence based on the TAC assay. These findings differ from previous observations among older children and adults in Europe and North America, suggesting that the effects of azithromycin on the bacterial microbiota may be specific to the age and geographic setting of its recipients.
Highlights
The use of antibiotics continues to rise globally
We assess the extent to which azithromycin influenced the composition of the bacterial microbiota in these infants by sequencing the V4 region of the bacterial 16S rRNA gene in DNA extracted from stool and testing for the presence of specific pathogen gene targets using PCR in a TaqMan array card (TAC) format
We found that azithromycin recipients were significantly less likely than placebo recipients to become colonised by bacterial pathogens – including enteroaggregative Escherichia coli, enteropathogenic E. coli, and Campylobacter – between days 0 and 14 (Table 2)
Summary
The use of antibiotics continues to rise globally. Numerous concerns have been raised regarding the long-term sequelae of this trend, including threats to populations, such as the emergence of antibiotic-resistant pathogens, and threats to individuals, such as an increased risk of metabolic disorders, asthma, and inflammatory bowel disease, among others[1,2,3]. In a recent cohort of 2–7 year-old children in Finland, treatment with a macrolide within the preceding 6 months was associated with a reduction in the diversity and relative maturity of the bacterial microbiota, as well as an increase in macrolide resistance genes[6]. Few previous studies have considered the influence of macrolide exposure on the composition of the bacterial microbiota within the context of placebo-controlled clinical trials using antibiotics. We recently performed a randomised placebo-controlled trial in Vellore, India, to examine the impact of a 3-day course of oral azithromycin on the immune response to a subsequent dose of monovalent type 3 oral poliovirus vaccine among seronegative 6–11 month-old infants[8]. We report on the impact of age on microbiota composition
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