Early-life gut microbiome and resistome trajectories and their determinants in a northern-Nigerian birth cohort

Thesis

Antimicrobial resistance (AMR) remains a critical threat to infant survival, especially in low- and middle-income countries (LMICs). As gut colonisation by resistant pathogens often precedes clinical infection and sepsis, understanding early-life microbiome and resistome development is essential. This thesis characterises the longitudinal codevelopment of the gut microbiome and resistome in a northern Nigerian birth cohort (n=87) from birth to 90 days of life, investigating the impact of clinical and environmental modulators in a resource-limited setting.

Utilising shotgun metagenomic sequencing of longitudinal faecal samples, with highintensity sampling during the first postnatal week, I employed Kaplan-Meier survival analysis and covariate-adjusted regression models to quantify the timing and determinants of antimicrobial resistance gene (ARG) acquisition. 

Results revealed a rapid early acquisition of ARGs within the first week of life. Although 10% of infants carried β-lactam or aminoglycoside ARGs at birth, prevalence rose to 90% by day 7. Near-universal β-lactam or aminoglycoside ARG prevalence was established by the second week, preceding most recorded infant antibiotic exposure. Taxonomic composition was dominated early by Escherichia and Klebsiella, with delayed Bifidobacterium colonisation in caesarean-section infants (first appearance day 14 vs days 0-7 in vaginally delivered infants). Delivery mode explained 6.2-7.8% of microbiome and resistome variation in the first week; however, this was attenuated by the third month, suggesting faster convergence than that reported from high-income countries. 

Contextual assessment of the cohort setting revealed routine postpartum antibiotic administration (contrary to global recommendations), constrained sanitation infrastructure, and compact household contact networks. These findings demonstrate that in high-exposure settings, AMR acquisition is contracted in the immediate neonatal window and driven by a multifactorial combination of maternal, healthcare, and environmental factors rather than infant-level antibiotic use alone. This thesis proposes a four-stage framework to guide intervention design, prioritising infection prevention, antibiotic stewardship, and support for microbial maturation, applied to LMIC.

Authors: Akpulu, CP

• DOI: 10.5287/ora-r8bogp8dd
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: antibiotic resistance genes carriage; resistome; gut microbiome; antimicrobial resistance; northern-nigeria; kano; neonates
• Subjects: Infant Health; Antimicrobial resistance; Metagenomics; Microbiology