Succession and determinants of the early life nasopharyngeal bacteriome in a South African birth cohort

Abstract Background : Bacteria colonizing the nasopharynx play a key role as gatekeepers of respiratory health. Yet, dynamics of early life nasopharyngeal (NP) bacterial profiles remain understudied in low-and-middle-income countries (LMICs), where children have a high prevalence of risk factors for lower respiratory tract infection. We investigated longitudinal changes in NP bacterial profiles, and associated exposures, among healthy infants from low-income households in South Africa. Methods : We used short fragment (V4 region) 16S rRNA gene amplicon sequencing to characterise NP bacterial profiles from 103 infants in a South African birth cohort, at monthly intervals from birth through the first 12 months of life and six-monthly thereafter until 30 months. Results: Corynebacterium and Staphylococcus were dominant colonizers at one month of life, however these were rapidly replaced by Moraxella- or Haemophilus -dominated profiles by four months. This succession was almost universal, and largely independent of a broad range of exposures Warm weather (summer), lower gestational age, maternal smoking, no day-care attendance, antibiotic exposure, or low height-for-age z score at 12 months were associated with higher alpha and beta diversity. Summer was also associated with higher relative abundances of Staphylococcus , Streptococcus , Neisseria or anaerobic gram-negative bacteria, whilst spring and winter were associated with higher relative abundances of Haemophilus or Corynebacterium , respectively. Maternal smoking was associated with higher relative abundances of Porphyromonas . Antibiotic therapy (or isoniazid prophylaxis for tuberculosis) was associated with higher relative abundance of anerobic taxa ( Porphyromonas , Fusobacterium and Prevotella ) and with lower relative abundances of health associated-taxa Corynebacterium and Dolosigranulum . HIV-exposure was associated with higher relative abundances of Klebsiella or Veillonella and lower relative abundances of an unclassified genus within the family Lachnospiraceae. Conclusions: In this intensively sampled cohort there was rapid and predictable replacement of early profiles dominated by health-associated Corynebacterium and Dolosigranulum with those dominated by Moraxella and Haemophilus , independent of exposures. Season and antibiotic exposure were key determinants of NP bacterial profiles. Understudied but highly prevalent exposures prevalent in LMICs, including maternal smoking and HIV-exposure, were associated with NP bacterial profiles.