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Development of Early Life Gut Resistome and Mobilome Across Gestational Ages and Microbiota-Modifying Treatments
30 Pages Posted: 20 Jan 2023
More...Abstract
Backgroun:d Gestational age (GA) and associated level of gastrointestinal tract maturation are major factors driving the initial gut microbiota composition. 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 conducted 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-naïve very preterm (n = 8), and antibiotic-naïve full-term (n = 10) infants. We collected stool samples on days of life 7, 28, 120, and 365, extracted DNA, and performed shotgun metagenome sequencing followed by 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 Klebsiellapneumoniae and K. aerogenes.
Interpretation: Prolonged hospitalisation, antibiotics, and probiotic intervention contribute to dynamic alterations in resistome and mobilome, gut microbiota characteristics relevant to infection risk.
Trial Registration: Clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT02197468).
Funding: Odd-Berg Group, Northern Norway Regional Health Authority. JBP acknowledges funding from the Data-Driven Life Science (DDLS) program supported by the Knut and Alice Wallenberg Foundation (KAW 2020.0239), the Centre for Antibiotic Resistance Research at the University of Gothenburg and grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-966073), and the Swedish Foundation for Strategic Research (FFL21-0174). V.K.P and A.B. acknowledge funding from the Trond Mohn Foundation via the Centre for New Antibacterial Strategies.
Declaration of Interests: The authors have declared that no conflict of interest exists.
Ethics Approval Statement: The study was approved by the Norwegian Regional Ethical Committee (2014/930/REK Nord) and informed written consent was obtained from all parents.
Keywords: Extremely preterm infants, Probiotics, Gestational age, gut microbiota, Resistome, Mobilome
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