Common antibiotics, azithromycin and amoxicillin, affect gut metagenomics within a household

Abstract

Background: The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.

Results: We characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.

Conclusions: As we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.

Keywords: Antibiotic courses; Antibiotic perturbations; Bacteriophage; Beta Lactam; Fecal; Gut; Macrolide; Metagenome; Microbiome; Microbiota; Resistome; Virome; Virus.

Fig. 1

Relative abundance (± standard error) of the most dominant bacterial genera among all amoxicillin treated participants, all azithromycin treated participants, and all non-household controls at each time point sampled. The y-axis represents the relative abundace of the dominant bacterial genera, and the x-axis represents the therapy they received and grouped by the time point sampled. Bars are colored by their antibiotic therapy group (amoxicillin, purple; azithromycin, red; non-household controls, gray). *denotes significance based on Kruskal–Wallis tests with correction via the Holm method

Fig. 2

Relative abundance (± standard error) of the most dominant bacterial genera among participants with 7-day azithromycin therapy (Azith 7d) and 3-day azithromycin therapy (Azith 3d) and their household and non-household controls. The y-axis represents the relative abundace of the dominant bacterial genera, and the x-axis represents the therapy they received, grouped by the time point sampled. Bars are colored by the therapy they received (Azith 7d, dark orange; Azith 3d, dark red; Azith 7d household controls, light orange; Azith 3d household controls light red; non-household controls, gray). *denotes significance based on Kruskal–Wallis tests with correction via the Holm method

Fig. 3

Relative abundance of the most dominant ARG drug classes among all amoxicillin treated participants, all azithromycin treated participants, and all non-household controls at each time point sampled. The y-axis represents the relative abundace of the dominant drug classes, and the x-axis represents the therapy they received grouped by the time point sampled. Boxplots are colored by their treatment status (amoxicillin, purple; azithromycin, red; non-household controls, gray). Abundace calcuated via reads per million (RPM) metric. *denotes significance based on Kruskal–Wallis tests with correction via the Holm method

Fig. 4

Relative abundance of the most dominant ARG drug classes among participants with 7-day azithromycin therapy (Azith 7d) and 3-day amoxicillin therapy (Azith 3d) and their household and non-household controls at each time point sampled. The y-axis represents the relative abundace of the dominant drug classes, and the x-axis represents the therapy they received grouped by the time point sampled. Boxplots are colored by their treatment status (Azith 7d, dark orange; Azith 3d, dark red; Azith 7d household controls, light orange; Azith 3d household controls light red; non-household controls, gray). Abundance calculated via reads per million (RPM) metric. *denotes significance based on Kruskal–Wallis tests with correction via the Holm method

Fig. 5

Relative abundace of the dominant bacteriophage families over time and antibiotic treatment. The y-axis represents the realtive abundace of the dominant phage families, and the x-axis represents the different subjects grouped by time and the therapy they received. Groups that received antibiotics, placebo (household controls), or no therapy (controls) are labeled accordingly