Development of early life gut resistome and mobilome across gestational ages and microbiota-modifying treatmentsResearch in context
Ahmed Bargheet,
Claus Klingenberg,
Eirin Esaiassen,
Erik Hjerde,
Jorunn Pauline Cavanagh,
Johan Bengtsson-Palme,
Veronika Kuchařová Pettersen
Affiliations
Ahmed Bargheet
Host-Microbe Interaction Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway; Paediatric Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Center for New Antibacterial Strategies, UiT The Arctic University of Norway, Tromsø, Norway
Claus Klingenberg
Paediatric Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Center for New Antibacterial Strategies, UiT The Arctic University of Norway, Tromsø, Norway; Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway
Eirin Esaiassen
Paediatric Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway
Erik Hjerde
Center for New Antibacterial Strategies, UiT The Arctic University of Norway, Tromsø, Norway; Department of Chemistry, Norstruct, UiT The Arctic University of Norway, Tromsø, Norway
Jorunn Pauline Cavanagh
Paediatric Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Center for New Antibacterial Strategies, UiT The Arctic University of Norway, Tromsø, Norway
Johan Bengtsson-Palme
Division of Systems Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, SE-412 96, Sweden; Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10A, Gothenburg, SE-413 46, Sweden; Centre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, Sweden
Veronika Kuchařová Pettersen
Host-Microbe Interaction Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway; Paediatric Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Center for New Antibacterial Strategies, UiT The Arctic University of Norway, Tromsø, Norway; Corresponding author. Host-Microbe Interaction Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Summary: Background: Gestational age (GA) and associated level of gastrointestinal tract maturation are major factors driving the initial gut microbiota composition in preterm infants. Besides, compared to term infants, premature infants often receive antibiotics to treat infections and probiotics to restore optimal gut microbiota. How GA, antibiotics, and probiotics modulate the microbiota’s core characteristics, gut resistome and mobilome, remains nascent. Methods: We analysed metagenomic data from a longitudinal observational study in six Norwegian neonatal intensive care units to describe the bacterial microbiota of infants of varying GA and receiving different treatments. The cohort consisted of probiotic-supplemented and antibiotic-exposed extremely preterm infants (n = 29), antibiotic-exposed very preterm (n = 25), antibiotic-unexposed very preterm (n = 8), and antibiotic-unexposed full-term (n = 10) infants. The stool samples were collected on days of life 7, 28, 120, and 365, and DNA extraction was followed by shotgun metagenome sequencing and bioinformatical analysis. Findings: The top predictors of microbiota maturation were hospitalisation length and GA. Probiotic administration rendered the gut microbiota and resistome of extremely preterm infants more alike to term infants on day 7 and ameliorated GA-driven loss of microbiota interconnectivity and stability. GA, hospitalisation, and both microbiota-modifying treatments (antibiotics and probiotics) contributed to an elevated carriage of mobile genetic elements in preterm infants compared to term controls. Finally, Escherichia coli was associated with the highest number of antibiotic-resistance genes, followed by Klebsiella pneumoniae and Klebsiella aerogenes. Interpretation: Prolonged hospitalisation, antibiotics, and probiotic intervention contribute to dynamic alterations in resistome and mobilome, gut microbiota characteristics relevant to infection risk. Funding: Odd-Berg Group, Northern Norway Regional Health Authority.
