In a groundbreaking genomic analysis of infant microbiomes in the UK, researchers have identified a specific bacterium that aids in digesting breast milk and shields babies’ guts from harmful pathogens.
Right after birth, newborns host one of three dominant bacteria in their guts, which could inform the creation of personalized probiotic therapies for infants, according to the study.
This major investigation, conducted by scientists from the Wellcome Sanger Institute, University College London (UCL), and the University of Birmingham, employed whole genome sequencing to study stool samples from 1,288 healthy infants, all under one month old, as part of the UK Baby Biome Study1.
The research, published today (September 6) in Nature Microbiology, discovered that one of these helpful bacteria is genetically tailored to effectively utilize nutrients present in breast milk. This indicates that it may be optimally suited for thriving in an infant’s microbiome. Furthermore, this bacterium is capable of preventing pathogens from taking residence in babies’ guts, showcasing its potential as a natural probiotic.
The implications of these findings could aid in creating infant formulas and therapeutic probiotics that feature the most effective natural bacterial strains for infants’ digestive health. Presently, most existing commercial infant probiotics employ a different bacterial strain that is not present in the early microbiomes of infants in developed nations like the UK and the US2,3.
Along with the two beneficial pioneer bacteria, the research also flagged a third bacterium that poses risks as it can lead to the growth of antibiotic-resistant bacteria. This may disrupt the development of an infant’s microbiome and elevate the risk of gut colonization by pathogens.
Looking ahead, researchers could potentially predict how an infant’s gut will evolve by mapping their gut microbiome profile right after birth to identify which pioneer bacteria are present. If necessary, tailored probiotics could be administered to encourage healthy microbiome growth and safeguard against harmful infections.
Additional studies, such as the Microbes, Milk, Mental Health and Me (4M) project, are essential for understanding the effects of these pioneer bacteria on health4. This initiative, co-led by the Wellcome Sanger Institute, forms part of the Children Growing Up in Liverpool study, which involves 10,000 mothers and infants. This extensive research aims to investigate how aspects like the infant gut microbiome and early dietary choices influence cognitive development, behavior, emotions, and mental wellness in later life.
The gut microbiome consists of a diverse ecosystem of millions of microbes crucial for human health and vital for the development of the immune system. It starts to establish itself right from birth, making the first month a key opportunity for introducing probiotics that could either restore or enhance the microbiome. However, prior to this study, there was a lack of detailed data illustrating how the microbiome matures during this early stage of life and which bacteria would be beneficial for healthy newborns.
Building on previous findings from the UK Baby Biome Study, which indicated that infants born vaginally possess a different microbiome compared to those delivered via cesarean section5, this research analyzed a larger dataset of 2,387 stool samples from 1,288 infants born in hospitals, along with some samples from their mothers. The research team discovered that all newborns could be categorized into one of three microbiome profiles, each defined by a distinctive dominant pioneer bacterium.
Within these pioneer bacteria, Bifidobacterium longum subsp. longum (B. longum) and Bifidobacterium breve (B. breve) were identified as beneficial since they facilitate the stable colonization of other helpful microbes, while Enterococcus faecalis (E. faecalis) was flagged as risky.
It was found that B. longum is transmitted from the mother’s gut during childbirth, but the researchers noted that B. breve is not transferred this way6. Additionally, they found that B. breve is genetically adapted to fully take advantage of the nutrients in breast milk and can inhibit harmful pathogens from settling in the babies’ guts.
Approximately 85% of the infants studied were breastfed in their initial weeks of life. The researchers observed that whether an infant was breastfed or formula-fed did not significantly impact the type of pioneer bacteria present in their gut, though antibiotic use did have an effect7. Furthermore, the study indicated that factors like maternal age and the number of times a mother has given birth might influence microbiome development; however, further investigation is required to explore this and its long-term health implications.
The researchers also found that a bacterium commonly found in commercial infant probiotics, Bifidobacterium longum subsp. infantis (B. infantis), was not among the pioneer bacteria and is rare in UK infants. This aligns with studies from other developed nations indicating a lack of naturally occurring B. infantis in early infant microbiomes2,3, suggesting that B. breve could serve as a more effective natural probiotic.
Dr. Yan Shao, the first author from the Wellcome Sanger Institute, stated: “Considering a newborn’s gut as an ecosystem that begins to take shape at birth, there was little knowledge about how microbes establish themselves initially before the UK Baby Biome Study’s findings. By analyzing high-resolution genomic data from over 1,200 babies, we’ve pinpointed three pioneer bacteria that play a pivotal role in developing the gut microbiota, enabling us to classify them into infant microbiome profiles. Understanding the composition of these ecosystems and their variations marks an important step toward crafting effective personalized interventions that can promote a healthy microbiome.”
Professor Louise Kenny, Lead Investigator of the Children Growing up in Liverpool study at the University of Liverpool, emphasized: “Choices regarding childbirth and breastfeeding are nuanced and deeply personal. It’s crucial to remember that no single option is universally best for every parent and child. We still lack a complete understanding of how the mode of birth and different infant feeding practices shape microbiome development and influence future health. This underscores the significance of this research; we must explore new avenues to ensure every child receives the optimal start in life.”
Professor Nigel Field, a co-author of the study from UCL, added: “While our research highlights three pioneer bacteria vital for the microbiome’s development in infants, it remains to be seen how these pioneer bacteria influence health and disease, both in childhood and later on. The UK Baby Biome Study is actively tracking participants to glean insights about this, and we now need even larger cohorts to investigate the role of the infant microbiome on overall health.”
Dr. Trevor Lawley, the senior author from the Wellcome Sanger Institute, noted: “The microbiome’s development in the early stages of life could have profound implications for a person’s health down the line. This period is also when infant probiotics could potentially be most effective, provided we identify which bacteria are necessary and relevant for specific populations. Our study highlights a particularly beneficial pioneer bacterium that can fully digest breast milk and shield newborns against harmful microbes.” This discovery could pave the way for enhanced probiotic therapies tailored for infants.
This study highlights the importance of a natural probiotic, which has the potential to settle in a child’s gut effectively. We hope that our publicly accessible research promotes careful selection of probiotic strains and the creation of innovative microbiome-based treatments grounded in genetic studies.
The researchers express their gratitude to the families who took part in the Baby Biome Study, as well as to the research midwives at the hospitals involved in recruitment.
- The UK Baby Biome Study is a comprehensive birth cohort study and biobank in the UK that includes ongoing follow-ups through electronic health records. Its goal is to explore how interactions between microorganisms, the immune system, and various clinical, social, and behavioral factors during pregnancy and early life impact health and diseases later on. For this study, stool samples were collected from newborns and their mothers, alongside vaginal swabs from mothers and umbilical cord blood. This research, funded by Wellcome, is a collaboration involving the Wellcome Sanger Institute, UCL, the University of Birmingham, and partnering hospitals.
- Ennis, D., Shmorak, S., Jantscher-Krenn, E. Yassour, M. (2024) conducted research on the late colonization of Bifidobacterium longum subsp. infantis in the infant gut, which occurs independently of the maternal milk HMO composition. Published in Nature Communications. DOI: 10.1038/s41467-024-45209-y
- Casaburi, G. et al. (2021) provided metagenomic insights into the structure and function of the infant microbiome across several sites in the United States. This was published in Scientific Reports. DOI: 10.1038/s41598-020-80583-9
- Researchers from Sanger Institute and their partners are compiling the world’s most comprehensive dataset on microbiome development to uncover new understandings about human health, with a particular focus on how the microbiome relates to mental health. This initiative is part of the new Children Growing Up in Liverpool (C-GULL) study, funded by Wellcome, which aims to monitor the health of 10,000 babies and their families from early pregnancy through childhood. The study seeks to explain how genetics, environment, and early life experiences impact long-term health, while also examining how elements such as the infant’s gut microbiome and early feeding practices influence brain development, behavior, emotions, and mental health later in life.
- The earlier research analyzed 1,679 gut bacteria samples from nearly 600 healthy infants and 175 mothers. It discovered that infants born vaginally possess a different gut microbiome compared to those delivered via caesarean section. The findings revealed that vaginally born infants predominantly acquire their gut bacteria from their mother’s gut rather than the vaginal canal, contrary to previous beliefs. Conversely, infants delivered by caesarean section did not receive maternal bacteria and instead had a greater presence of bacteria associated with hospital environments. By the time the children reached one year of age, the differences in gut bacteria between the two delivery methods mostly subsisted.
- While it was established that B. longum was transmitted from the mother’s gut during delivery, B. breve did not follow this route. The specific source of B. breve transmission remains unidentified, but researchers propose that it might come from other parts of the mother, such as the skin microbiome. Additionally, B. breve was found to be more prevalent among children whose mothers identified as Asian.
- This study suggests that the administration of antibiotics increases the likelihood of E. faecalis colonizing infants’ guts, although the long-term health impacts are still uncertain. Profiling a newborn’s microbiome and customizing probiotic treatments could offer advantages for infants with such a microbiome profile.
Dr. Trevor Lawley, a co-founder and Chief Scientific Officer of Microbiotica, a biopharmaceutical company focused on developing precise live biotherapeutic products, especially for immuno-oncology and inflammatory bowel disease, is also involved in this research.
Funding for this research came from Wellcome and the Wellcome Sanger Institute.
