Changes in the intestinal microbiota following the administration of azithromycin in a randomised placebo-controlled trial among infants in south India

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.

Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

“…Recent randomized controlled trials indicate that even short-term antibiotic use may lead to significant changes in the gut microbiota [38,39]. Antibiotic exposure and low microbiome diversity have been increasingly recognized as important risk factors for poor transplant outcomes including GVHD and bacterial infection [3,6,[8][9][10][11][12][13]40].…”

The mutual interplay of gut microbiota, diet and human disease

“…A marked transformation in the gut microbial community occurs after weaning from the mother and the introduction of solid foods, with an increase in the number of butyrate producers, that is Bacteroides and Clostridium species . Antibiotics use significantly impacts the evolution of the infant gut microbiota by increasing Proteobacteria and lowering Actinobacteria populations , decreasing the overall diversity and selecting for drug‐resistant bacteria. Moreover, some epidemiological studies correlated the antibiotic consumption in early life with the increased risk of allergic disease (i.e.…”

Dissecting the collateral damage of antibiotics on gut microbes

“…Recently more attention has been given to this collateral damage of antibiotics on the gut microbiota and thereby on the host’s wellbeing. In vivo studies highlight links between the long-term microbiota compositional changes and host dysbiosis, including the development of allergic, metabolic, immunological and inflammatory diseases 5-8,10,11,19-21 . While uncovering the direct effects of different antibiotics on our gut flora is critical to improve general health, technical difficulties hamper routine testing of antibiotic susceptibility in anaerobes 22,23 .…”

“…We established that both kill different subsets of prevalent commensal bacteria, and cause cell lysis in specific cases. This species-specific activity challenges the long-standing divide of antibiotics into bactericidal and bacteriostatic, and provides a possible explanation for the strong impact of macrolides on the gut microbiota composition in animals 5-8 and humans 9-11 . To mitigate the collateral damage of macrolides and tetracyclines on gut commensals, we exploited the fact that drug combinations have species-specific outcomes in bacteria 12 and sought marketed drugs, which could antagonize the activity of these antibiotics in abundant gut commensal species.…”