The abundance and selection of antibiotic resistance genes: A metagenomic study based on wastewater and human gut data.

Sammanfattning

Antibiotic resistance is a global issue, with many consequences for the individualperson and society as a whole. Studying potential new genes conferring resistance(latent ARGs) and the flow of resistance genes through environments could be crucialfor the prevention and control of ARGs. This project aimed firstly to investigate howantibiotic usage affects new antibiotic resistance genes in the human gut. A metagenomicpipeline including mapping of reads and statistical models using a study of 12healthy individuals treated with three broad-spectrum antibiotics enabled analysisof ARGs and taxonomy abundances. It was shown that after treatment with thebroad-spectrum antibiotics, several latent ARGs were more abundant in the shortterm, implying the potential selection of these ARGs. The change in ARGs can notbe ruled out as being due to the recolonization of fast-growing bacterial species, normallycarrying such genes, as also the taxonomy composition was largely affected.This effect was not seen on the last sampling day, after 180 days, in which only onesingle ARG was found at higher abundance. The short-term effect could, nevertheless,impact the spread of ARGs due to the potential for these ARGs to spread inthe disrupted microbiota.Secondly, this project aimed to investigate the flow of ARGs between the human gutand wastewater. For this, a large number of metagenomic samples were used. Similarlyto the first part, a metagenomic pipeline was utilized for ARG and taxonomyanalysis. Contrary to previous findings, the results implied that ARGs flow fromthe human gut to the wastewater, while not the other way around. Furthermore,pathogenic presence was highest for ARGs found at high prevalence in both thehuman gut and wastewater. Interestingly, ARGs present only in wastewater weremore prevalent in pathogens compared to ARGs present only in the human gut.This implies that the spread of ARGs to pathogens could be linked to presence inwastewater environments. Moreover, the taxonomy of the human gut and wastewaterdiffered. The results of this project can inform several future research directions,from broadening the data of longitudinal studies to a deeper dive into the flow ofARGs.