Antibiotics Exert Sustained Effect on Gut Microbiome

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A metagenomics study of the effects of azithromycin and amoxicillin on the gut microbiome found sustained alteration in microbial communities and increases in putative resistance genes, and suggests a spill-over effect on the microbiome of untreated housemates.

"That some of the most abundant bacteria in the gut are impacted in response to these antibiotics suggest that the effects of these antibiotics on gut microbiome health may be substantial and long-lasting," remarked study lead author Jessica Chopyk, PhD, Department of Pathology, University of California San Diego, San Diego, CA, and colleagues.

The investigators recruited 56 participants, comprising 24 housemate pairs and 8 individuals from different, separate households. Participants received either amoxicillin or azithromycin, or placebo (vitamin C) once daily for either 3 or 7 days. Fecal samples were collected on day 0, 3, 7, week 8, and at 6 months.A total of 282 samples were sequenced.

The bacterial genera most abundant in all participants included Bacteriodes, Bifidobacterium, Ruminococcus, Eubacterium, Prevotella, Faecalibacterium, and Blautia. The azithromyin-treated participants demonstrated significantly reduced amounts of Bifidobacteria compared to those receiving placbo; and these were significantly lower at day 7 and week 8 than in those receiving amoxicillin. Those receiving amoxicillin demonstrated a significantly higher relative abundance of Bacterioides after 3 days of treatment than the non-household controls.

A possible spill-over effect was observed in the untreated housemates of those receiving azithromycin for either 3 or 7 days, as they also exhibited statistically significantly lower relative abundance of Bifidobacterium at week 8.

"Given the association of stable Bifidobacterium populations with improved gut health, these results could have important implications of the gut health of more than just the individual receiving antibiotic treatment," Chopyk and colleagues suggested.

The investigators assessed the presence of genes that have been associated with antibiotic resistance (to over 81 drug classes) in the samples taken before, during and after the amoxicillin or azithromycin exposure.They identified an average of 2% or greater increases in a range of antibiotic resistance genes.

Those receiving azithromycin exhibited a significantly higher abundance of genes associated with resistance to macrolide, lincosamide and stretogramin compared to non-household controls at days 7, week 8 and month 6.In contrast, azithromycin exposure was associated with reduction in genes related to resistance to glycopeptides at week 8, and in genes resistant to peptides at day 7 and month 6.There were no "spill over" effects on the amounts of putative antibiotic resistance genes, however, in either the household or non-household placebo controls.

The investigators also assessed change in the phage community composition in response to the antibiotic exposure.They report no significant correlation between the abundance of the three major families of Caudovirales and duration of antibiotic use.

Although they had suspected that transmission of lytic phages from the treated participant could be a mechanism for the apparent "spill over" of reduction in Bifidobacteria in the housemate, this was not supported in their virome analysis. An alternative explanation, they offered, is just noise in the system, since Bifidobacteria relative abundances were low.

"While much has been revealed over time about the impacts of common antibiotics on the gut microbiome, there still is a knowledge gap as to the potential medium-term changes that can be observed in individuals taking the same antibiotic," Chopyk and colleagues acknowledged.