Antibiotic perturbation and the development of the human microbiome over the first two years of life

Background/Question/Methods

Young children are often treated with antibiotics. How this affects microbiome development is largely unknown. Here, we investigated the spatial and temporal extent of antibiotic perturbation of the developing microbiome using a prospective cohort study design. We followed 15 healthy mother-infant pairs, starting at birth and continuing for 2 years. From each infant, fecal, oral, and skin swab specimens were collected at baseline (on each of 3 consecutive days each month) and in the event of antibiotic treatment (daily before, during, and for one week after treatment, then weekly until the next baseline collection). From each mother, fecal, oral, skin swab, vaginal swab and breast milk specimens were collected at postpartum months 1, 7, 13, 19, and 24. All samples were surveyed for bacterial taxa using amplified 16S rRNA gene sequencing. Selected samples were also surveyed using assembly-driven metagenomics, which provided insight into bacterial population-level dynamics around antibiotic perturbation events.

Results/Conclusions

Six of the infants received no courses of systemically absorbed antibiotics in the first 2 years of life. Among the 9 infants who were treated, the number of courses ranged from 1 to 10. Thus, for each course of antibiotics, we were able to make 2 types of comparisons involving samples collected during and after treatment: (1) to pre-treatment baseline samples from the same treated subject and (2) to baseline samples from antibiotic-naïve subjects of the same age. A total of 4,150 unique samples were collected for the study. We found that body site and age were the primary drivers of bacterial community composition, and that maturation and personalization of community composition occurred at different rates and to differing degrees depending on body site. During antibiotic treatment, community composition was, in certain cases, profoundly altered; however, after treatment, communities also appeared to be highly resilient (including cases of population recovery after local near-extinction). Intriguingly, certain aspects of the response to antibiotics seemed to depend on the infant’s prior history (e.g., delivery mode; antibiotic exposures). These results provide preliminary insight into the scale of antibiotic perturbation of the developing microbiota, and into the conditions favoring resiliency.