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. 2021 Jan-Dec;13(1):1-19.
doi: 10.1080/19490976.2021.1900995.

Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment

Kang Kang  1   2 , Lejla Imamovic  1 , Maria-Anna Misiakou  1 , Maria Bornakke Sørensen  1 , Yoshitaro Heshiki  2   3 , Yueqiong Ni  2 , Tingting Zheng  2   3 , Jun Li  2   4   5 , Mostafa M H Ellabaan  1 , Marta Colomer-Lluch  1 , Anne A Rode  6   7 , Peter Bytzer  6   7 , Gianni Panagiotou  2   3   8 , Morten O A Sommer  1
Affiliations

Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment

Kang Kang et al. Gut Microbes. 2021 Jan-Dec.

Abstract

Oral antibiotics are commonly prescribed to non-hospitalized adults. However, antibiotic-induced changes in the human gut microbiome are often investigated in cohorts with preexisting health conditions and/or concomitant medication, leaving the effects of antibiotics not completely understood. We used a combination of omic approaches to comprehensively assess the effects of antibiotics on the gut microbiota and particularly the gut resistome of a small cohort of healthy adults. We observed that 3 to 19 species per individual proliferated during antibiotic treatment and Gram-negative species expanded significantly in relative abundance. While the overall relative abundance of antibiotic resistance gene homologs did not significantly change, antibiotic-specific gene homologs with presumed resistance toward the administered antibiotics were common in proliferating species and significantly increased in relative abundance. Virome sequencing and plasmid analysis showed an expansion of antibiotic-specific resistance gene homologs even 3 months after antibiotic administration, while paired-end read analysis suggested their dissemination among different species. These results suggest that antibiotic treatment can lead to a persistent expansion of antibiotic resistance genes in the human gut microbiota and provide further data in support of good antibiotic stewardship.Abbreviation: ARG - Antibiotic resistance gene homolog; AsRG - Antibiotic-specific resistance gene homolog; AZY - Azithromycin; CFX - Cefuroxime; CIP - Ciprofloxacin; DOX - Doxycycline; FDR - False discovery rate; GRiD - Growth rate index value; HGT - Horizontal gene transfer; NMDS - Non-metric multidimensional scaling; qPCR - Quantitative polymerase chain reaction; RPM - Reads per million mapped reads; TA - Transcriptional activity; TE - Transposable element; TPM - Transcripts per million mapped reads.

Keywords: Gut microbiome; antibiotic resistance; antibiotic treatment; mobile element; phage; virome.

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Figures

Figure 1.
Figure 1.
Microbial community diversity and dissimilarity
Figure 2.
Figure 2.
The relative abundances of different species categories in different antibiotic treatment periods
Figure 3.
Figure 3.
DNA relative abundance and transcriptional activity (TA) of AsRG
Figure 4.
Figure 4.
Transcriptional activity (TA) (a) and DNA abundance (b) of mobile and non-mobile AsRGs
Figure 5.
Figure 5.
Horizontal gene transfer (HGT) potential for AsRGs mediated by bacteriophage
Figure 6.
Figure 6.
HGT-supporting read counts over time and the host species of the mate contigs
See this image and copyright information in PMC

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