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dc.contributor.advisorPettersen, Veronika
dc.contributor.authorBargheet, Ahmed
dc.date.accessioned2025-07-03T08:58:07Z
dc.date.available2025-07-03T08:58:07Z
dc.date.issued2025-08-21
dc.description.abstractAntimicrobial resistance (AMR) is a growing global health concern, particularly in vulnerable populations such as infants. The gut microbiota, which plays a crucial role in health and disease, is shaped by early-life factors like birth mode, feeding type, antibiotic exposure, probiotics, and hospitalisation. However, how these factors influence antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in the infant gut remains poorly understood. This thesis investigates how early-life exposures affect the resistome (collection of ARGs) and mobilome (collection of MGEs) and assesses whether probiotics can help mitigate AMR. By integrating shotgun metagenomics, bioinformatics, statistical modelling, and machine learning, this research provides a comprehensive analysis across diverse infant cohorts. The findings show that <i>Escherichia coli</i> plays a dominant role in shaping the infant resistome and mobilome. Paper I demonstrates that probiotic supplementation in extremely preterm infants reduces pathogenic bacteria, promotes microbiota maturation, and lowers ARG abundance. Paper II, a large-scale meta-analysis, reveals that birth mode, gestational age, feeding type, and geography significantly influence resistome and mobilome composition. Notably, over half of ARGs were linked to plasmids in bacteria like <i>Escherichia coli</i> and <i>Enterococcus faecalis</i>, highlighting the role of horizontal gene transfer in AMR spread. Paper III reinforces the benefits of probiotics, showing that in full-term infants, they slow the replication of <i>Escherichia coli</i>, reduce ARG and MGE loads, and contribute to a healthier gut microbiota. These insights provide a foundation for microbiota-targeted strategies to combat AMR in early life. By improving AMR surveillance and informing probiotic-based interventions, this research supports efforts to reduce antibiotic resistance and promote healthier microbial development in infants.en_US
dc.description.doctoraltypeph.d.en_US
dc.description.popularabstractAntibiotic resistance is a growing global health challenge, especially in infants. This thesis explores how early-life factors, such as birth mode, antibiotic exposure, probiotics, and hospitalisation, shape gut bacteria and influence the spread of antibiotic-resistant genes and mobile genetic elements. Using cutting-edge bioinformatics and statistical modelling, this research analysed thousands of infant samples to uncover key patterns in gut bacteria development. The findings highlight the crucial role of Escherichia coli in spreading antibiotic resistance in early life. Probiotic supplementation was shown to promote a healthier gut microbiota, reduce harmful bacteria, and lower the presence of resistance genes. These insights can help improve antibiotic resistance monitoring and inform future strategies to support infant health, such as tailored probiotic treatments and public health policies aimed at reducing antimicrobial resistance from birth.en_US
dc.identifier.urihttps://hdl.handle.net/10037/37387
dc.language.isoengen_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.relation.haspart<p>Paper I: Bargheet, A., Klingenberg, C., Esaiassen, E., Hjerde, E., Cavanagh, J.P., Bengtsson-Palme, J. & Pettersen, V.K. (2023). Development of early life gut resistome and mobilome across gestational ages and microbiota-modifying treatments. <i>eBioMedicine, 92</i>, 104613. Also available in Munin at <a href=https://hdl.handle.net/10037/30066>https://hdl.handle.net/10037/30066</a>. <p>Paper II: Bargheet, A., Noordzij, H.T., Ponsero, A.J., Jian, C., Korpela, K., Valles-Colomer, M., … Pettersen, V.K. (2025). Dynamics of the gut resistome and mobilome in early life: a meta-analysis. <i>eBioMedicine, 114</i>, 105630. Also available in Munin at <a href=https://hdl.handle.net/10037/37383>https://hdl.handle.net/10037/37383</a>. <p>Paper III: Bargheet, A., Justine, M., Moyo, S.J., Löhr, I.H., Blomberg, B., Langeland, N., Klingenberg, C. & Pettersen, V.K. Probiotic-induced modulation of pathobionts abundance, resistome, and mobilome in infants gut. (Manuscript).en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2025 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.subjectExtremely preterm infantsen_US
dc.subjectProbioticsen_US
dc.subjectGestational ageen_US
dc.subjectGut microbiotaen_US
dc.subjectResistomeen_US
dc.subjectMobilomeen_US
dc.subjectPathobiontsen_US
dc.titleDynamics of Infant Gut Resistome and Mobilome: Impact of Gestational Age, Antibiotics, Probiotics, and Other Early-Life Factorsen_US
dc.typeDoctoral thesisen_US
dc.typeDoktorgradsavhandlingen_US


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Attribution 4.0 International (CC BY 4.0)
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