NEW YORK – An international team has traced gut microbial community assembly in UK infants using longitudinal metagenomic sequencing and identified three distinct early community structures that are each associated with a different pioneering bacterial species.
"This is the first large-scale cohort study to delineate the community state (enterotype-like) structures in the neonatal gut microbiota," Wellcome Sanger Institute researcher Yan Shao said in an email, adding that "we observed different microbiome development trajectories depending on the type of pioneer bacteria acquired by 1-week-old babies."
These and other results mark the "first human observational evidence of the priority effects of microbial species in shaping early-life microbiota assembly," Shao explained.
As part of the UK Baby Biome Study, Shao and colleagues from the Wellcome Sanger Institute, University College London, and the University of Birmingham used whole-genome sequencing to characterize gut microbes found in nearly 2,400 stool samples from 1,288 healthy infants under the age of 1 month. The set included samples collected over time for a subset of infants as well as samples from 183 mother-infant pairs.
From the metagenomic sequence data, the team flagged "primary colonizer" species, Enterococcus faecalis, Bifidobacterium longum subspecies longum, or B. breve, that coincided with one of three resulting gut microbiome community states — work that appeared in Nature Microbiology on Friday.
"[W]e have identified three pioneer bacteria that drive the development of the gut microbiota, allowing us to group them into infant microbiome profiles," Shao said in a statement. "Being able to see the makeup of these ecosystems and how they differ is the first step in developing effective personalized interventions to help support a healthy microbiome."
While the E. faecalis-enriched community state was marked by instability and increased representation by potentially pathogenic microbes, for example, the investigators saw signs that community states centered on pioneering Bifidobacterium species were relatively stable and had features consistent with pathogen resistance and effective utilization of breast milk nutrients.
That pattern appeared particularly pronounced for the B. breve-dominated community state, which the team examined with pathogen colonization experiments in a germ-free mouse model.
From these and other follow-up experiments, along with findings from smaller studies reported in the past, the authors suggested that "[m]aternal seeding of microbial metabolizers of the specialized bioactives in breast milk probably represents an [evolutionarily] conserved strategy to prime human gut microbiota assembly with primary colonizers with the highest likelihood for priority effects, such as B. breve and, to a lesser extent, B. longum."
The findings hinted at the possibility of providing a rational probiotic boost to formula formulations, rather than the B. infantis species that is more commonly used in commercial probiotics, Shao explained, noting that the study's findings also hint at the possibility of targeting microbiota-based therapeutic strategies to infants based on their early microbiome profiles.
Building on prior research that found a role for delivery methods on early infant gut microbiome development, the team also focused in on other early microbial community features that coincided with vaginal or cesarean-section birth. The analyses revealed maternal and perinatal factors with apparent ties to infant gut microbiome community states and the primary colonizers present — from infant sex to maternal age, ethnicity, and birth history.
Even so, the authors explained that it remains to be seen if and how each infant gut microbial community state relates to the children's outcomes over the longer term.
"While our study has shortlisted three pioneer bacteria as important for babies' microbiome development, it remains to be determined if and how different pioneer bacteria affect health and diseases, both in childhood and later in life," coauthor Nigel Field, a global health researcher at UCL, said in a statement. He added that UK Baby Biome Study investigators are "actively following up participants to give clues about this, and now even bigger cohorts are needed to investigate the role of the infant microbiome on health."