Microbiota succession throughout life from the cradle to the grave

The early life microbiome plays critical roles in host development, shaping long-term outcomes including brain functioning. It is not known which initial infant colonizers elicit optimal neurodevelopment; thus, this study investigated the association between gut microbiome succession from the first week of life and head circumference growth (HCG), the earliest validated marker for neurodevelopment. Fecal samples were collected weekly from a preterm infant cohort during their neonatal intensive care unit stay and subjected to 16S rRNA gene sequencing for evaluating gut microbiome composition, in conjunction with clinical data and head circumference measurements. Preterm infants with suboptimal HCG trajectories had a depletion in the abundance/prevalence of Bacteroidota and Lachnospiraceae, independent of morbidity and caloric restriction. The severity of gut microbiome depletion matched the timing of significant HCG pattern separation between study groups at 30-week postmenstrual age demonstrating a potential mediating relationship resultant from clinical practices. Consideration of the clinical variables indicated that optimal infant microbiome succession is primarily driven by dispersal limitation (i.e., delivery mode) and secondarily by habitat filtering (i.e., antibiotics and enteral feeding). Bacteroidota and Lachnospiraceae are known core taxa of the adult microbiome, with roles in dietary glycan foraging, beneficial metabolite production and immunity, and our work provides evidence that their integration into the gut microbiome needs to occur early for optimal neurodevelopment.

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment.

Newborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood. Here we validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities. This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. This microbial effect is amplified by prior gestation in a maternal obesogenic or vaginal dysbiotic environment where placental and fetal ileum development are altered, and an augmented immune response increases rates of offspring mortality. Collectively, we describe a translationally relevant model to examine the defined role of specific human microbial communities on offspring health outcomes, and demonstrate that the prenatal environment dramatically shapes the postnatal response to inoculation. Exposure at birth to maternal microbiota has significant effects on offspring health and development. Here, the authors validate a model where inoculation of mice at birth with human vaginal microbiota produces significant effects on offspring health that are further amplified by an unhealthy prenatal environment.

The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model.

Mother-to-infant microbiota transmission and infant microbiota development across multiple body sites.

Can maternal-child microbial seeding interventions improve the health of infants delivered by Cesarean section?

Summary Background Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. Methods Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth. Findings Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study. Conclusions The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth. Funding C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.

Elizabeth Ackley

Papers

Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding