Researchers Alexandra Zhernakova, Trishla Sinha and their their colleagues from the have now completed one of the world's most comprehensive studies of the pregnancy and early-life gut microbiome by following 714 mother–infant pairs from the Lifelines NEXT birth cohort, as published today in Nature.
Current research suggests that the infant gut is sterile prior to birth, but is rapidly colonized thereafter through exposures to microbes in the infant’s environment. Over the first year of life, the gut microbiome then undergoes substantial changes as the infant is exposed to new microbes from other individuals, food sources and their surroundings. This early microbial evolution could have major impacts on later health, but characterizing this critical phase has been challenging up to now.
It may seem obvious that mothers influence the development of their babies’ gut microbiome. What was less clear was how this happens. By combining thousands of microbiome profiles from the maternal gut, vaginal microbiome, breast milk and infant gut with detailed clinical, lifestyle and environmental data, this study shows that the maternal gut microbiome is the primary source of bacteria colonizing the infant gut. Relatively few bacteria appear to come directly from the mother’s vaginal microbiome or breast milk, but they include functionally important microbes. For example, the researchers identified transmission of Bifidobacterium breve from the maternal vaginal microbiome to the infant gut.
The study further confirms mode of delivery (vaginal vs cesarian section) and feeding mode (human milk, mixed or formula feeding) as key factors shaping the infant gut microbiome. Delivery mode not only influences which microbial species are present, it appears to affect the infant gut microbiome’s potential to metabolize carbohydrates in human milk and formula. Similarly, feeding mode influenced both presence of microbes and their capacity to produce compounds that may be involved in communication between the gut and the nervous system.
The study also identified maternal pre-pregnancy exposures such as smoking, maternal infections during pregnancy, birth-related factors such as duration of ruptured membranes, and the presence of siblings and pets in the household. We found associations with several factors that occurred before pregnancy, including smoking, even when the smoking had occurred much earlier in life, before pregnancy. We also found associations with events during pregnancy, such as infections, and events during childbirth. This suggests that the development of a child’s microbiome is not determined solely by what happens after birth, but may already begin much earlier. Finally, and very importantly, the research linked the maternal gut microbiome to infant eczema, highlighting the potential importance of maternal microbial health for a child's future health.
Together, these findings provide a more comprehensive understanding of how early-life experiences shape the developing infant gut microbiome, and the study provides an exceptionally rich resource for investigating how early-life microbiome development influences health later in life. Future work will extend our analyses to 1,500 mother–infant pairs and incorporate other microbial niches, such as the oral microbiome. We will also focus on understanding the mechanisms underlying the associations identified in this study by integrating analyses of the developing immune system. Finally, we aim to investigate how microbial changes during pregnancy and early life influence infant and child health by continuing to follow these children throughout childhood and, hopefully, beyond.
This study is a collaboration, bringing together colleagues from across the UMCG, including the departments of Genetics, Paediatrics, Obstetrics and Gynaecology, Health Sciences, Primary and Long-Term Care, Lifelines, and the UMCG Innovation Center, together with several international collaborators.
Zhernakova: ‘We are deeply grateful to the midwives and obstetricians across the Northern Netherlands for their dedication to participant recruitment and sample collection, and especially to all participating families who generously shared their time, trust and biological samples throughout this longitudinal study. Without their commitment, this research would not have been possible.’
The Lifelines NEXT cohort was established through a collaboration between UMCG and several academic and industrial partners. Nestlé Research contributed to the development of the cohort through scientific discussions and long-term collaboration, in addition to providing financial support.
