Antibiotic Treatment Drives the Diversification of the Human Gut Resistome

Jun Li,Elizabeth A Rettedal,Eric Van Der Helm,Mostafa Ellabaan,Gianni Panagiotou,Morten O.A Sommer

doi:10.1016/j.gpb.2018.12.003

Jun Li, Elizabeth A Rettedal + Show 4 more

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https://doi.org/10.1016/j.gpb.2018.12.003

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Despite the documented antibiotic-induced disruption of the gut microbiota, the impact of antibiotic intake on strain-level dynamics, evolution of resistance genes, and factors influencing resistance dissemination potential remains poorly understood. To address this gap we analyzed public metagenomic datasets from 24 antibiotic treated subjects and controls, combined with an in-depth prospective functional study with two subjects investigating the bacterial community dynamics based on cultivation-dependent and independent methods. We observed that short-term antibiotic treatment shifted and diversified the resistome composition, increased the average copy number of antibiotic resistance genes, and altered the dominant strain genotypes in an individual-specific manner. More than 30% of the resistance genes underwent strong differentiation at the single nucleotide level during antibiotic treatment. We found that the increased potential for horizontal gene transfer, due to antibiotic administration, was ∼3-fold stronger in the differentiated resistance genes than the non-differentiated ones. This study highlights how antibiotic treatment has individualized impacts on the resistome and strain level composition, and drives the adaptive evolution of the gut microbiota.

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The human intestines are densely populated by diverse microbial inhabitants, which collectively constitute the gut microbiota
We analyzed public metagenomic data from a longitudinal study of 18 cefprozil treated and 6 healthy control volunteers [12] that aimed to investigate whether the initial taxonomic composition of the gut microbiota is associated with the reshaped post-antibiotic microbiota
Using these data we investigated the dynamics and diversification of the resistome, strain-level selection, variation of the dissemination potential of antibiotic resistance, and the single-nucleotide level differentiation under antibiotic treatment

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Introduction

The human intestines are densely populated by diverse microbial inhabitants, which collectively constitute the gut microbiota. Besides influencing physiology of the digestive tract, the gut microbiota affects development, immunity, and metabolism of the host [1]. External forces, including antibiotic treatment or dietary intake, shape the composition of the gut microbiota with the potential for rapid changes, thereby affecting the microbe–host homeostasis [2,3]. Previous metagenomic studies have revealed the influence of antibiotic administration on the gut microbiota in various ways, including (1) altering the global taxonomic and functional composition or the diversity of the gut microbiota [7,8,9,10,11], (2) increasing the abundance of bacteria resistant to the administered antibiotic [12], (3) expanding the reservoir of resistance genes (resistome) [13], or (4) increasing the load of particular antibiotic resistance genes (ARGs) [11,14]. How antibiotic exposure influences strain-level variation within the gut microbiome remains poorly understood

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